Post on 06-Apr-2018
transcript
8/3/2019 Excitatory Synapse
1/15
Excitatory synapse
From Wikipedia, the free encyclopedia
A diagram of a typical central nervous system synapse. The spheres located in the upper neuron
contain neurotransmitters that fuse with the presynaptic membrane and release neurotransmitters
into the synaptic cleft. These neurotransmitters bind to receptors located on the postsynaptic
membrane of the lower neuron, and, in the case of an excitatory synapse, may lead to a
depolarization of the postsynaptic cell.
An excitatory synapse is a synapse in which an action potentialin a presynaptic neuron increases
the probability of an action potential occurring in a postsynaptic cell. Neurons form networks
through which nerve impulses travel, each neuron often making numerous connections withother cells. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory
influences exceeds that of the inhibitory influences, the neuron will fire, that is, it will generate
a new action potential at itsaxon hillock, thus transmitting the information to yet another cell.[1]
This phenomenon is known as an excitatory postsynaptic potential (EPSP). It may occur via
direct contact between cells (i.e., via gap junctions), as in an electrical synapse, but most
commonly occurs via the vesicularrelease ofneurotransmitters from the presynaptic axonterminal into the synaptic cleft, as in a chemical synapse.[2]
The excitatory neurotransmitters, the most common of which is glutamate, then migrate via
diffusion to thedendritic spine of the postsynaptic neuron and bind a specific transmembrane
receptorprotein that triggers thedepolarizationof that cell.[1] Depolarization, a deviation from a
neurons resting membrane potentialtowards its threshold potential, increases the likelihood ofan action potential and normally occurs with the influx of positively chargedsodium (Na+) ions
into the postsynaptic cell through ion channelsactivated by neurotransmitter binding.
Contents
[hide]
1 Chemical vs electrical synapses 2 Synaptic transmission
3 Responses of the postsynaptic neuron
4 Types of excitatory neurotransmitters
http://en.wikipedia.org/wiki/Synapsehttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/wiki/Neuronhttp://en.wikipedia.org/wiki/Axon_hillockhttp://en.wikipedia.org/wiki/Axon_hillockhttp://en.wikipedia.org/wiki/Axon_hillockhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Annual_Review_of_Biochemistry-0http://en.wikipedia.org/wiki/EPSPhttp://en.wikipedia.org/wiki/Gap_junctionhttp://en.wikipedia.org/wiki/Electrical_synapsehttp://en.wikipedia.org/wiki/Vesicle_(biology_and_chemistry)http://en.wikipedia.org/wiki/Vesicle_(biology_and_chemistry)http://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Axonhttp://en.wikipedia.org/wiki/Chemical_synapsehttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Journal_of_Cell_Science-1http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Journal_of_Cell_Science-1http://en.wikipedia.org/wiki/Glutamatehttp://en.wikipedia.org/wiki/Glutamatehttp://en.wikipedia.org/wiki/Diffusionhttp://en.wikipedia.org/wiki/Dendritic_spinehttp://en.wikipedia.org/wiki/Dendritic_spinehttp://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Depolarizationhttp://en.wikipedia.org/wiki/Depolarizationhttp://en.wikipedia.org/wiki/Depolarizationhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Annual_Review_of_Biochemistry-0http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Annual_Review_of_Biochemistry-0http://en.wikipedia.org/wiki/Membrane_potentialhttp://en.wikipedia.org/wiki/Membrane_potentialhttp://en.wikipedia.org/wiki/Threshold_potentialhttp://en.wikipedia.org/wiki/Threshold_potentialhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Ion_channelshttp://en.wikipedia.org/wiki/Ion_channelshttp://en.wikipedia.org/wiki/Excitatory_synapsehttp://en.wikipedia.org/wiki/Excitatory_synapse#Chemical_vs_electrical_synapseshttp://en.wikipedia.org/wiki/Excitatory_synapse#Synaptic_transmissionhttp://en.wikipedia.org/wiki/Excitatory_synapse#Responses_of_the_postsynaptic_neuronhttp://en.wikipedia.org/wiki/Excitatory_synapse#Types_of_excitatory_neurotransmittershttp://en.wikipedia.org/wiki/File:Synapse_Illustration2_tweaked.svghttp://en.wikipedia.org/wiki/File:Synapse_Illustration2_tweaked.svghttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/wiki/Neuronhttp://en.wikipedia.org/wiki/Axon_hillockhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Annual_Review_of_Biochemistry-0http://en.wikipedia.org/wiki/EPSPhttp://en.wikipedia.org/wiki/Gap_junctionhttp://en.wikipedia.org/wiki/Electrical_synapsehttp://en.wikipedia.org/wiki/Vesicle_(biology_and_chemistry)http://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Axonhttp://en.wikipedia.org/wiki/Chemical_synapsehttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Journal_of_Cell_Science-1http://en.wikipedia.org/wiki/Glutamatehttp://en.wikipedia.org/wiki/Diffusionhttp://en.wikipedia.org/wiki/Dendritic_spinehttp://en.wikipedia.org/wiki/Receptor_(biochemistry)http://en.wikipedia.org/wiki/Depolarizationhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Annual_Review_of_Biochemistry-0http://en.wikipedia.org/wiki/Membrane_potentialhttp://en.wikipedia.org/wiki/Threshold_potentialhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Ion_channelshttp://en.wikipedia.org/wiki/Excitatory_synapsehttp://en.wikipedia.org/wiki/Excitatory_synapse#Chemical_vs_electrical_synapseshttp://en.wikipedia.org/wiki/Excitatory_synapse#Synaptic_transmissionhttp://en.wikipedia.org/wiki/Excitatory_synapse#Responses_of_the_postsynaptic_neuronhttp://en.wikipedia.org/wiki/Excitatory_synapse#Types_of_excitatory_neurotransmittershttp://en.wikipedia.org/wiki/Synapse8/3/2019 Excitatory Synapse
2/15
o 4.1 Acetylcholine
o 4.2 Glutamate
o 4.3 Catecholamines
o 4.4 Serotonin
o 4.5 Histamine
5 Diseaseo 5.1 Excitotoxicity
5.1.1 Pathophysiology 5.1.2 Treatment
o 5.2 Related neurodegenerative diseases
6 See also
7 References
[edit] Chemical vs electrical synapses
Animation showing the function of a chemical synapse.There are two different kinds of synapses present within the human brain: chemical and
electrical. Chemical synapses are by far the most prevalent and are the main playerinvolved in excitatory synapses. Electrical synapses, the minority, allow direct, passiveflow of electrical current through special intercellular connections called gap junctions. [3]
These gap junctions allow for virtually instantaneous transmission of electrical signals
through direct passive flow of ions between neurons (transmission can be bidirectional).The main goal of electrical synapses is to synchronize electrical activity among
populations of neurons[3]. The first electrical synapse was discovered in acrayfish
nervous system.[3]
Chemical synaptic transmission is the transfer of neurotransmitters orneuropeptidesfrom
a presynaptic axon to a postsynaptic axon. [3] Unlike an electrical synapse, the chemical
synapses are separated by a space called the synaptic cleft, typically measured between
15 and 25 nm. Transmission of an excitatory signal involves several steps outlined below.
[edit] Synaptic transmission
1. In neurons that are involved in chemical synaptic transmission, neurotransmitters are
synthesized either in the neuronal cell body, or within the presynaptic terminal,
depending on the type of neurotransmitter being synthesized and the location of enzymes
http://en.wikipedia.org/wiki/Excitatory_synapse#Acetylcholinehttp://en.wikipedia.org/wiki/Excitatory_synapse#Glutamatehttp://en.wikipedia.org/wiki/Excitatory_synapse#Catecholamineshttp://en.wikipedia.org/wiki/Excitatory_synapse#Serotoninhttp://en.wikipedia.org/wiki/Excitatory_synapse#Histaminehttp://en.wikipedia.org/wiki/Excitatory_synapse#Diseasehttp://en.wikipedia.org/wiki/Excitatory_synapse#Excitotoxicityhttp://en.wikipedia.org/wiki/Excitatory_synapse#Pathophysiologyhttp://en.wikipedia.org/wiki/Excitatory_synapse#Treatmenthttp://en.wikipedia.org/wiki/Excitatory_synapse#Related_neurodegenerative_diseaseshttp://en.wikipedia.org/wiki/Excitatory_synapse#See_alsohttp://en.wikipedia.org/wiki/Excitatory_synapse#Referenceshttp://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=1http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Caridoid_escape_reactionhttp://en.wikipedia.org/wiki/Caridoid_escape_reactionhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Neuropeptideshttp://en.wikipedia.org/wiki/Neuropeptideshttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Synaptic_clefthttp://en.wikipedia.org/wiki/Synaptic_clefthttp://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=2http://en.wikipedia.org/wiki/File:Synapse.theora.ogvhttp://en.wikipedia.org/wiki/File:Synapse.theora.ogvhttp://en.wikipedia.org/wiki/Excitatory_synapse#Acetylcholinehttp://en.wikipedia.org/wiki/Excitatory_synapse#Glutamatehttp://en.wikipedia.org/wiki/Excitatory_synapse#Catecholamineshttp://en.wikipedia.org/wiki/Excitatory_synapse#Serotoninhttp://en.wikipedia.org/wiki/Excitatory_synapse#Histaminehttp://en.wikipedia.org/wiki/Excitatory_synapse#Diseasehttp://en.wikipedia.org/wiki/Excitatory_synapse#Excitotoxicityhttp://en.wikipedia.org/wiki/Excitatory_synapse#Pathophysiologyhttp://en.wikipedia.org/wiki/Excitatory_synapse#Treatmenthttp://en.wikipedia.org/wiki/Excitatory_synapse#Related_neurodegenerative_diseaseshttp://en.wikipedia.org/wiki/Excitatory_synapse#See_alsohttp://en.wikipedia.org/wiki/Excitatory_synapse#Referenceshttp://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=1http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Caridoid_escape_reactionhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Neuropeptideshttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Synaptic_clefthttp://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=28/3/2019 Excitatory Synapse
3/15
involved in its synthesis. These neurotransmitters are stored insynaptic vesicles that
remain bound near the membrane by calcium-influenced proteins.
2. In order to trigger the process of chemical synaptic transmission, upstream activity causesan action potential to invade the presynaptic terminal.
3. This depolarizing current reaches the presynaptic terminal, and the membrane
depolarization that it causes there initiates the opening ofvoltage-gated calcium channelspresent on the presynaptic membrane.
4. There is high concentration ofcalcium in the synaptic cleft between the two participating
neurons (presynaptic and postsynaptic). This difference in calcium concentration betweenthe synaptic cleft and the inside of the presynaptic terminal establishes a strong
concentration gradient that drives the calcium into the presynaptic terminal upon opening
of these voltage-gated calcium channels. This influx of calcium into the presynaptic
terminal is necessary for neurotransmitter release.
5. After entering the presynaptic terminal, the calcium binds a protein called synaptotagmin,
which is located on the membrane of the synaptic vesicles. This protein interacts with
other proteins called SNAREs in order to induce vesicle fusion with the presynaptic
membrane. As a result of this vesicle fusion, the neurotransmitters that had beenpackaged into the synaptic vesicle are released into the synapse, where they diffuse
across the synaptic cleft.6. These neurotransmitters bind to a variety of receptors on the postsynaptic cell membrane.
In response to neurotransmitter binding, these postsynaptic receptors can undergo
conformational changes that may open a transmembrane channel subunit either directly,
or indirectly via a G-Protein signaling pathway. The selective permeability of thesechannels allow certain ions to move along their electrochemical gradients, inducing a
current across the postsynaptic membrane that determines an excitatory or inhibitory
response.
[3]
[edit] Responses of the postsynaptic neuron
When neurotransmitters reach the postsynaptic neuron of an excitatory synapse, these
molecules can bind to two possible types of receptors that are clustered in a protein-richportion of the postsynaptic cytoskeleton called the Postsynaptic density (PSD).[2]
Ionotropic receptors, which are also referred to asligand-gated ion channels, contain a
transmembrane domain that acts as an ion channel and can directly open after binding of
a neurotransmitter. Metabotropic receptors, which are also called G-protein-coupledreceptors, act on an ion channel through the intracellular signaling of a molecule called a
G protein. Each of these channels has a specific reversal potential, Erev, and each receptoris selectively permeable to particular ions that flow either into or out of the cell in orderto bring the overall membrane potential to this reversal potential. [3] If a neurotransmitter
binds to a receptor with a reversal potential that is higher than the threshold potential for
the postsynaptic neuron, the postsynaptic cell will be more likely to generate an actionpotential and an excitatory postsynaptic potential will occur (EPSP). On the other hand, if
the reversal potential of the receptor to which the neurotransmitter binds is lower than the
threshold potential, an inhibitory postsynaptic potentialwill occur (IPSP).[4]
http://en.wikipedia.org/wiki/Synaptic_vesiclehttp://en.wikipedia.org/wiki/Synaptic_vesiclehttp://en.wikipedia.org/wiki/Synapsinhttp://en.wikipedia.org/wiki/Voltage-gated_calcium_channelshttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Synaptotagminhttp://en.wikipedia.org/wiki/SNARE_(protein)http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=3http://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Postsynaptic_densityhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Journal_of_Cell_Science-1http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Journal_of_Cell_Science-1http://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/G-protein-coupled_receptorhttp://en.wikipedia.org/wiki/G-protein-coupled_receptorhttp://en.wikipedia.org/wiki/G_proteinhttp://en.wikipedia.org/wiki/Reversal_potentialhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Inhibitory_postsynaptic_potentialhttp://en.wikipedia.org/wiki/Inhibitory_postsynaptic_potentialhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-National_Center_for_Biotechnology_Information-3http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-National_Center_for_Biotechnology_Information-3http://en.wikipedia.org/wiki/Synaptic_vesiclehttp://en.wikipedia.org/wiki/Synapsinhttp://en.wikipedia.org/wiki/Voltage-gated_calcium_channelshttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Synaptotagminhttp://en.wikipedia.org/wiki/SNARE_(protein)http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=3http://en.wikipedia.org/wiki/Cytoskeletonhttp://en.wikipedia.org/wiki/Postsynaptic_densityhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Journal_of_Cell_Science-1http://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/G-protein-coupled_receptorhttp://en.wikipedia.org/wiki/G-protein-coupled_receptorhttp://en.wikipedia.org/wiki/G_proteinhttp://en.wikipedia.org/wiki/Reversal_potentialhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Inhibitory_postsynaptic_potentialhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-National_Center_for_Biotechnology_Information-38/3/2019 Excitatory Synapse
4/15
Although the receptors at an excitatory synapse strive to bring the membrane potential
towards their own specific Erev, the probability that the single stimulation of an excitatory
synapse will raise the membrane potential past threshold and produce an action potentialis not very high. Therefore, in order to achieve threshold and generate an action potential,
the postsynaptic neuron has the capacity to add up all of the incoming EPSPs based on
the mechanism ofsummation, which can occur in time and space. Temporal summationoccurs when a particular synapse is stimulated at a high frequency, which causes the
postsynaptic neuron to sum the incoming EPSPs and thus increases the chance of the
neuron firing an action potential. In a similar way, the postsynaptic neuron can sumtogether EPSPs from multiple synapses with other neurons in a process called spatial
summation.[3]
[edit] Types of excitatory neurotransmitters
[edit] Acetylcholine
Acetylcholine(ACh) is an excitatory, small-molecule neurotransmitter involved insynaptic transmission at neuromuscular junctions controlling the vagus nerve and cardiacmuscle fibers, as well as in the skeletal and visceral motor systems and various sites
within the central nervous system.[3] This neurotransmitter crosses the synaptic cleft and
binds to a variety of postsynaptic receptors depending on thespecies, but all of thesereceptors depolarize the postsynaptic membrane and thus classify ACh as an excitatory
neurotransmitter.[5]
[edit] Glutamate
Glutamate is a small, amino acid neurotransmitter, and is the primary excitatory
neurotransmitter at almost all synapses in the central nervous system. This molecule
binds multiple postsynaptic receptors including theNMDA receptor, AMPA receptor,andkainate receptors. These receptors are all cationchannels that allow positively
charged ions such as Na+, K+, and sometimes Ca2+ into the postsynaptic cell, causing a
depolarization that excites the neuron.[3]
[edit] Catecholamines
The catecholamines, which include Epinephrine,Norepinephrine, andDopamine, are
excitatory biogenic amineneuromodulators that are derived from the amino acidtyrosineand serve as excitatory neurotransmitters are various locations in the central nervous
system as well as theperipheral nervous system. Epinephrine and norepinephrine, also
called adrenaline and noradrenaline, respectively, bind a number of G-protein-coupledreceptors that induce their depolarizing effects on the postsynaptic cell in various ways,
including activating and inactivating certain K+ channels. Epinephrine is found in the
lateral tegmental system,medulla,hypothalamus, and thalamusof the central nervoussystem, but their function is not fully understood. Norepinephrine is found in thebrain
stem and is involved in sleep and wakefulness, feeding behavior, and attention.
http://en.wikipedia.org/wiki/Summation_(neurophysiology)http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=4http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=5http://en.wikipedia.org/wiki/Acetylcholinehttp://en.wikipedia.org/wiki/Acetylcholinehttp://en.wikipedia.org/wiki/Neuromuscular_junctionhttp://en.wikipedia.org/wiki/Vagus_nervehttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Motor_systemhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Specieshttp://en.wikipedia.org/wiki/Specieshttp://en.wikipedia.org/wiki/Specieshttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-WormBook-4http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=6http://en.wikipedia.org/wiki/Glutamic_acidhttp://en.wikipedia.org/wiki/NMDA_receptorhttp://en.wikipedia.org/wiki/AMPA_receptorhttp://en.wikipedia.org/wiki/Kainate_receptorhttp://en.wikipedia.org/wiki/Kainate_receptorhttp://en.wikipedia.org/wiki/Cationhttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=7http://en.wikipedia.org/wiki/Catecholaminehttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Norepinephrinehttp://en.wikipedia.org/wiki/Norepinephrinehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Neuromodulationhttp://en.wikipedia.org/wiki/Neuromodulationhttp://en.wikipedia.org/wiki/Tyrosinehttp://en.wikipedia.org/wiki/Tyrosinehttp://en.wikipedia.org/wiki/Peripheral_nervous_systemhttp://en.wikipedia.org/wiki/Adrenalinehttp://en.wikipedia.org/wiki/Tegmentumhttp://en.wikipedia.org/wiki/Medulla_oblongatahttp://en.wikipedia.org/wiki/Medulla_oblongatahttp://en.wikipedia.org/wiki/Medulla_oblongatahttp://en.wikipedia.org/wiki/Hypothalamushttp://en.wikipedia.org/wiki/Thalamushttp://en.wikipedia.org/wiki/Thalamushttp://en.wikipedia.org/wiki/Brain_stemhttp://en.wikipedia.org/wiki/Brain_stemhttp://en.wikipedia.org/wiki/Summation_(neurophysiology)http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=4http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=5http://en.wikipedia.org/wiki/Acetylcholinehttp://en.wikipedia.org/wiki/Neuromuscular_junctionhttp://en.wikipedia.org/wiki/Vagus_nervehttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Cardiac_musclehttp://en.wikipedia.org/wiki/Motor_systemhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Specieshttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-WormBook-4http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=6http://en.wikipedia.org/wiki/Glutamic_acidhttp://en.wikipedia.org/wiki/NMDA_receptorhttp://en.wikipedia.org/wiki/AMPA_receptorhttp://en.wikipedia.org/wiki/Kainate_receptorhttp://en.wikipedia.org/wiki/Cationhttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=7http://en.wikipedia.org/wiki/Catecholaminehttp://en.wikipedia.org/wiki/Epinephrinehttp://en.wikipedia.org/wiki/Norepinephrinehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Neuromodulationhttp://en.wikipedia.org/wiki/Tyrosinehttp://en.wikipedia.org/wiki/Peripheral_nervous_systemhttp://en.wikipedia.org/wiki/Adrenalinehttp://en.wikipedia.org/wiki/Tegmentumhttp://en.wikipedia.org/wiki/Medulla_oblongatahttp://en.wikipedia.org/wiki/Hypothalamushttp://en.wikipedia.org/wiki/Thalamushttp://en.wikipedia.org/wiki/Brain_stemhttp://en.wikipedia.org/wiki/Brain_stem8/3/2019 Excitatory Synapse
5/15
Dopamine binds to G-protein-coupled receptors in many areas of the brain, especially the
corpus striatumwhere it mediates the synaptic transmission that underlies the
coordination of body movements.[3]
[edit] Serotonin
Serotonin is an excitatory neurotransmitter that regulates sleep and wakefulness and isfound in neurons of the raphe region of the pons and upper brain stem, which extend into
the forebrain. Serotonin binds a number of receptors, including the 5-HT3 receptors,
which are ligand-gated ion channels that allow the passage of cations in order todepolarize the membrane potential of the postsynaptic neuron that they reside on.[3]
Levels of serotonin activity that are lower than normal have been linked to a variety of
symptoms, especially depression, which is why many antidepressant drugs act to increaseserotonin activity.[6]
[edit] Histamine
Histamineacts as an excitatory neurotransmitter by binding G-protein coupled receptorsin neurons of the hypothalamus. These neurons project into many regions of the brain and
spinal cord, allowing histamine to mediate attention, arousal, and allergic responses.[3] Of
the four types of histamine receptors (H1 - H4), H3 is found in the central nervous system
and is responsible for regulating histamine effects on neurotransmission.[7]
[edit] Disease
Excitatory synapses have a fundamental role in information processing within the brain
and throughout the peripheral nervous system. Usually situated on dendritic spines, or
neuronal membrane protrusions on which glutamate receptors and postsynaptic densitycomponents are concentrated, excitatory synapses aid in the electrical transmission of
neuronal signals.[1] The physical morphology of synapses is crucial in understanding their
function, and it is well documented that the inappropriate loss of synaptic stability leadsto the disruption of neuronal circuits and the resulting neurological diseases. Although
there are innumerable different causes for differentneurodegenerativeillnesses, such as
genetic dispositions ormutations, the normal aging process,parasiticand viral causes, ordrug use, many can be traced back to dysfunctional signaling between the neurons
themselves, often at the synapse.[3]
[edit] Excitotoxicity
Main Article: Excitotoxicity
[edit] Pathophysiology
Since glutamate is the most common excitatory neurotransmitter involved in synapticneuronal transmission, it follows that disruptions in the normal functioning of these
http://en.wikipedia.org/wiki/Corpus_striatumhttp://en.wikipedia.org/wiki/Corpus_striatumhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=8http://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Raphe_nucleihttp://en.wikipedia.org/wiki/Forebrainhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-The_Human_Brain_Mind_Center-5http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=9http://en.wikipedia.org/wiki/Histaminehttp://en.wikipedia.org/wiki/Histaminehttp://en.wikipedia.org/wiki/Allergyhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Pathophysiology_of_the_Endocrine_System-6http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=10http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Annual_Review_of_Biochemistry-0http://en.wikipedia.org/wiki/Neurodegenerationhttp://en.wikipedia.org/wiki/Neurodegenerationhttp://en.wikipedia.org/wiki/Neurodegenerationhttp://en.wikipedia.org/wiki/Mutationshttp://en.wikipedia.org/wiki/Parasitehttp://en.wikipedia.org/wiki/Parasitehttp://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=11http://en.wikipedia.org/wiki/Excitotoxicityhttp://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=12http://en.wikipedia.org/wiki/Corpus_striatumhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=8http://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Raphe_nucleihttp://en.wikipedia.org/wiki/Forebrainhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-The_Human_Brain_Mind_Center-5http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=9http://en.wikipedia.org/wiki/Histaminehttp://en.wikipedia.org/wiki/Allergyhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Pathophysiology_of_the_Endocrine_System-6http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=10http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Annual_Review_of_Biochemistry-0http://en.wikipedia.org/wiki/Neurodegenerationhttp://en.wikipedia.org/wiki/Mutationshttp://en.wikipedia.org/wiki/Parasitehttp://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=11http://en.wikipedia.org/wiki/Excitotoxicityhttp://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=128/3/2019 Excitatory Synapse
6/15
pathways can have severe detrimental effects on the nervous system. A major source of
cellular stress is related to glutaminergic overstimulation of a postsynaptic neuron via
excessive activation of glutamate receptors (i.e.,NMDA and AMPA receptors), a processknown as excitotoxicity, which was first discovered accidentally by D. R. Lucas and J. P.
Newhouse in 1957 during experimentation on sodium-fed lab mice.[3]
Under normal conditions, extracellular glutamate levels are held under strict control bysurrounding neuronal and glial cellmembrane transporters, rising to a concentration of
about 1 mM and quickly falling to resting levels.[8] These levels are maintained via the
recycling of glutamate molecules in the neuronal-glial cell process known as theglutamate-glutamine cycle, in which glutamate issynthesized from its precursor
glutamine in a controlled manner in order to maintain an adequate supply of the
neurotransmitter. [3] However, when glutamate molecules in the synaptic cleft cannot be
degraded or reused, often due to dysfunction of the glutamate-glutamine cycle, theneuron becomes significantly overstimulated, leading to a neuronal cell death pathway
known as apoptosis. Apoptosis occurs primarily via the increased intracellular
concentrations of calcium ions, which flow into the cytosol through the activated
glutamate receptors and lead to the activation ofphospholipases,endonucleases,proteases, and thus the apoptotic cascade. Additional sources of neuronal cell death
related to excitotoxicity involve energy rundown in the mitochondriaand increasedconcentrations of reactive oxygenand nitrogen species within the cell.[3]
[edit] Treatment
Excitotoxic mechanisms are often involved in other conditions leading to neuronal
damage, including hypoglycemia, trauma, stroke,seizures, and many neurodegenerative
diseases, and thus have important implications in disease treatment. Recent studies havebeen performed that incorporate glutamatereceptor antagonists and excitotoxic cascade
disruptors in order to decrease stimulation of postsynaptic neurons, although thesetreatments are still undergoing active research.[9]
[edit] Related neurodegenerative diseases
Alzheimers Disease (AD) is the most common form of neurodegenerative dementia, orloss of brain function, and was first described by German psychiatrist and
neuropathologist Alois Alzheimer in 1907. 9. [10]Diagnosis of the disease often stems
from clinical observation as well as analysis of family history and other risk factors, andoften includes symptoms such as memory impairment and problems with language,
decision-making, judgment, and personality.[11] The primary neurological phenomena that
lead to the above symptoms are often related to signaling at excitatory synapses, oftendue to excitotoxicity, and stem from the presence ofamyloid plaques and neurofibrillarytangles, as well as neuronal cell death and synaptic pruning. The principle drug
treatments on the market deal with antagonizing glutamate (NMDA) receptors at
neuronal synapses, and inhibiting the activity ofacetylcholinesterase. This treatment aimsto limit the apoptosis of cerebral neurons caused by various pathways related to
excitotoxicity, free radicals, and energy rundown. A number of labs are currently
http://en.wikipedia.org/wiki/NMDA_Receptorhttp://en.wikipedia.org/wiki/AMPA_Receptorhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Glial_cellhttp://en.wikipedia.org/wiki/Membrane_transport_proteinhttp://en.wikipedia.org/wiki/Membrane_transport_proteinhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Science_Daily-7http://en.wikipedia.org/wiki/Glutamate-glutamine_cyclehttp://en.wikipedia.org/wiki/Chemical_synthesishttp://en.wikipedia.org/wiki/Chemical_synthesishttp://en.wikipedia.org/wiki/Glutaminehttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Phospholipasehttp://en.wikipedia.org/wiki/Phospholipasehttp://en.wikipedia.org/wiki/Endonucleasehttp://en.wikipedia.org/wiki/Proteasehttp://en.wikipedia.org/wiki/Mitochondriahttp://en.wikipedia.org/wiki/Mitochondriahttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Reactive_nitrogen_specieshttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=13http://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Trauma_(medicine)http://en.wikipedia.org/wiki/Strokehttp://en.wikipedia.org/wiki/Strokehttp://en.wikipedia.org/wiki/Seizurehttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Biochemical_Pharmacology-8http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=14http://en.wikipedia.org/wiki/Alzheimer%E2%80%99s_Diseasehttp://en.wikipedia.org/wiki/Dementiahttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Disease_Management_Project-9http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Disease_Management_Project-9http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Pub-Med_Health:_Diseases_and_Conditions-10http://en.wikipedia.org/wiki/Amyloid_plaquehttp://en.wikipedia.org/wiki/Amyloid_plaquehttp://en.wikipedia.org/wiki/Neurofibrillary_tanglehttp://en.wikipedia.org/wiki/Neurofibrillary_tanglehttp://en.wikipedia.org/wiki/Acetylcholinesterasehttp://en.wikipedia.org/wiki/NMDA_Receptorhttp://en.wikipedia.org/wiki/AMPA_Receptorhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Glial_cellhttp://en.wikipedia.org/wiki/Membrane_transport_proteinhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Science_Daily-7http://en.wikipedia.org/wiki/Glutamate-glutamine_cyclehttp://en.wikipedia.org/wiki/Chemical_synthesishttp://en.wikipedia.org/wiki/Glutaminehttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Phospholipasehttp://en.wikipedia.org/wiki/Endonucleasehttp://en.wikipedia.org/wiki/Proteasehttp://en.wikipedia.org/wiki/Mitochondriahttp://en.wikipedia.org/wiki/Reactive_oxygen_specieshttp://en.wikipedia.org/wiki/Reactive_nitrogen_specieshttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Neuroscience.2C_4th_ed.-2http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=13http://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Trauma_(medicine)http://en.wikipedia.org/wiki/Strokehttp://en.wikipedia.org/wiki/Seizurehttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Biochemical_Pharmacology-8http://en.wikipedia.org/w/index.php?title=Excitatory_synapse&action=edit§ion=14http://en.wikipedia.org/wiki/Alzheimer%E2%80%99s_Diseasehttp://en.wikipedia.org/wiki/Dementiahttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Disease_Management_Project-9http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Pub-Med_Health:_Diseases_and_Conditions-10http://en.wikipedia.org/wiki/Amyloid_plaquehttp://en.wikipedia.org/wiki/Neurofibrillary_tanglehttp://en.wikipedia.org/wiki/Neurofibrillary_tanglehttp://en.wikipedia.org/wiki/Acetylcholinesterase8/3/2019 Excitatory Synapse
7/15
focusing on the prevention of amyloid plaques and other AD symptoms, often via the use
of experimental vaccines, although this area of research is yet in its infancy.[10]
Histological brain sample of the Substantia Nigra in Parkinson's disease, showing the presence of
Lewy bodies and other signs of neurodegeneration.
Parkinsons Disease (PD) is a neurodegenerative disease resulting from the apoptosis ofdopaminergic neurons in the central nervous system, especially thesubstantia nigra, as
well as heightened response to the excitatory neurotransmitter, glutamate (i.e.,
excitotoxicity).[12] While the most obvious symptoms are related to motor skills,prolonged progression of the disease can lead to cognitive and behavioral problems aswell as dementia. Although the mechanism of apoptosis in the brain is not entirely clear,
speculation associates cell death with abnormal accumulation ofubiquitinated proteins in
cell occlusions known as Lewy bodies, as well as hyperstimulation of neuronal NMDAreceptors with excessive glutamate neurotransmitter via the aforementioned pathway.[12]
Like Alzheimers, Parkinsons Disease lacks a cure. Therefore, in addition to lifestyle
changes and surgery, the goal of pharmaceutical drugs used in the treatment of PDpatients is to control symptoms and limit, when possible, the progression of the disease.
Levodopa (L-DOPA), the most widely used treatment of PD, is converted to dopamine in
the body and helps to relieve the effect of decreased dopaminergic neurons in the central
nervous system. Other dopamine agonistshave been administered to patients in an effortto mimic dopamines effect at excitatory synapses, binding its receptors and causing the
desired postsynaptic response.[13]
http://en.wikipedia.org/wiki/Vaccinehttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Disease_Management_Project-9http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Disease_Management_Project-9http://en.wikipedia.org/wiki/Parkinson%E2%80%99s_Diseasehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Parkinsonism_and_Related_Disorders-11http://en.wikipedia.org/wiki/Ubiquitinhttp://en.wikipedia.org/wiki/Lewy_bodyhttp://en.wikipedia.org/wiki/Lewy_bodyhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Parkinsonism_and_Related_Disorders-11http://en.wikipedia.org/wiki/Levodopahttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Pub-Med_Health:_Diseases_and_Conditions_.E2.80.93_PD-12http://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Pub-Med_Health:_Diseases_and_Conditions_.E2.80.93_PD-12http://en.wikipedia.org/wiki/File:Histological_sample_of_Substantia_nigra_in_Parkinson%27s_disease.jpghttp://en.wikipedia.org/wiki/File:Histological_sample_of_Substantia_nigra_in_Parkinson%27s_disease.jpghttp://en.wikipedia.org/wiki/Vaccinehttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Disease_Management_Project-9http://en.wikipedia.org/wiki/Parkinson%E2%80%99s_Diseasehttp://en.wikipedia.org/wiki/Dopaminehttp://en.wikipedia.org/wiki/Substantia_nigrahttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Parkinsonism_and_Related_Disorders-11http://en.wikipedia.org/wiki/Ubiquitinhttp://en.wikipedia.org/wiki/Lewy_bodyhttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Parkinsonism_and_Related_Disorders-11http://en.wikipedia.org/wiki/Levodopahttp://en.wikipedia.org/wiki/Agonisthttp://en.wikipedia.org/wiki/Excitatory_synapse#cite_note-Pub-Med_Health:_Diseases_and_Conditions_.E2.80.93_PD-128/3/2019 Excitatory Synapse
8/15
8/3/2019 Excitatory Synapse
9/15
Ligand-gated ion channel
8/3/2019 Excitatory Synapse
10/15
From Wikipedia, the free encyclopedia
Neurotransmitter-gated ion-channel
transmembrane region
Ligand-gated ion channel
Identifiers
Symbol Neur_chan_memb
Pfam PF02932
InterPro IPR006029
PROSITE PDOC00209
SCOP 1cek
TCDB 1.A.9
OPM family 14
OPM protein 2bg9
[show]Available protein structures:
Neurotransmitter-gated ion-channel ligand
binding domain
http://en.wikipedia.org/wiki/Pfamhttp://pfam.sanger.ac.uk/family?acc=PF02932http://en.wikipedia.org/wiki/InterProhttp://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR006029http://en.wikipedia.org/wiki/PROSITEhttp://www.expasy.org/cgi-bin/prosite-search-ac?PDOC00209http://en.wikipedia.org/wiki/Structural_Classification_of_Proteinshttp://scop.mrc-lmb.cam.ac.uk/scop/search.cgi?tlev=fa;&pdb=1cekhttp://en.wikipedia.org/wiki/TCDBhttp://www.tcdb.org/search/result.php?tc=1.A.9http://en.wikipedia.org/wiki/Orientations_of_Proteins_in_Membranes_databasehttp://opm.phar.umich.edu/families.php?superfamily=14http://en.wikipedia.org/wiki/Orientations_of_Proteins_in_Membranes_databasehttp://opm.phar.umich.edu/protein.php?search=2bg9http://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/File:LGIC.pnghttp://en.wikipedia.org/wiki/Pfamhttp://pfam.sanger.ac.uk/family?acc=PF02932http://en.wikipedia.org/wiki/InterProhttp://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR006029http://en.wikipedia.org/wiki/PROSITEhttp://www.expasy.org/cgi-bin/prosite-search-ac?PDOC00209http://en.wikipedia.org/wiki/Structural_Classification_of_Proteinshttp://scop.mrc-lmb.cam.ac.uk/scop/search.cgi?tlev=fa;&pdb=1cekhttp://en.wikipedia.org/wiki/TCDBhttp://www.tcdb.org/search/result.php?tc=1.A.9http://en.wikipedia.org/wiki/Orientations_of_Proteins_in_Membranes_databasehttp://opm.phar.umich.edu/families.php?superfamily=14http://en.wikipedia.org/wiki/Orientations_of_Proteins_in_Membranes_databasehttp://opm.phar.umich.edu/protein.php?search=2bg9http://en.wikipedia.org/wiki/Ligand-gated_ion_channel8/3/2019 Excitatory Synapse
11/15
Identifiers
Symbol Neur_chan_LBD
Pfam PF02931
InterPro IPR006202
PROSITE PDOC00209
SCOP 1lxg
[show]Available protein structures:
Ligand-gated ion channels (LGICs) are one type of ionotropic receptor orchannel-linkedreceptor. They are a group oftransmembraneion channelsthat are opened or closed in response
to the binding of a chemical messenger (i.e., a ligand),[1] such as a neurotransmitter.[2]
The binding site ofendogenousligands on LGICs protein complexes are normally located on a
different portion of the protein (an allosteric binding site) compared to where the ion conductionpore is located. The direct link between ligand binding and opening or closing of the ion channel,
which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of
metabotropic receptors, which usesecond messengers. LGICs are also different fromvoltage-gated ion channels(which open and close depending on membrane potential), and stretch-
activated ion channels (which open and close depending on mechanical deformation of the cell
membrane).[2][3]
http://en.wikipedia.org/wiki/Pfamhttp://pfam.sanger.ac.uk/family?acc=PF02931http://en.wikipedia.org/wiki/InterProhttp://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR006202http://en.wikipedia.org/wiki/PROSITEhttp://www.expasy.org/cgi-bin/prosite-search-ac?PDOC00209http://en.wikipedia.org/wiki/Structural_Classification_of_Proteinshttp://scop.mrc-lmb.cam.ac.uk/scop/search.cgi?tlev=fa;&pdb=1lxghttp://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/Ion_channel_linked_receptorshttp://en.wikipedia.org/wiki/Ion_channel_linked_receptorshttp://en.wikipedia.org/wiki/Ion_channel_linked_receptorshttp://en.wikipedia.org/wiki/Transmembranehttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-0http://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-Purves-1http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-Purves-1http://en.wikipedia.org/wiki/Endogeny#Biologyhttp://en.wikipedia.org/wiki/Endogeny#Biologyhttp://en.wikipedia.org/wiki/Allosteric_regulationhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/Second_messenger_systemhttp://en.wikipedia.org/wiki/Second_messenger_systemhttp://en.wikipedia.org/wiki/Second_messenger_systemhttp://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttp://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttp://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttp://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttp://en.wikipedia.org/wiki/Membrane_potentialhttp://en.wikipedia.org/wiki/Stretch-activated_ion_channelhttp://en.wikipedia.org/wiki/Stretch-activated_ion_channelhttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-Purves-1http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid15157178-2http://en.wikipedia.org/wiki/File:2bg9_opm.gifhttp://en.wikipedia.org/wiki/Pfamhttp://pfam.sanger.ac.uk/family?acc=PF02931http://en.wikipedia.org/wiki/InterProhttp://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR006202http://en.wikipedia.org/wiki/PROSITEhttp://www.expasy.org/cgi-bin/prosite-search-ac?PDOC00209http://en.wikipedia.org/wiki/Structural_Classification_of_Proteinshttp://scop.mrc-lmb.cam.ac.uk/scop/search.cgi?tlev=fa;&pdb=1lxghttp://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/Ion_channel_linked_receptorshttp://en.wikipedia.org/wiki/Ion_channel_linked_receptorshttp://en.wikipedia.org/wiki/Transmembranehttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-0http://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-Purves-1http://en.wikipedia.org/wiki/Endogeny#Biologyhttp://en.wikipedia.org/wiki/Allosteric_regulationhttp://en.wikipedia.org/wiki/Metabotropic_receptorhttp://en.wikipedia.org/wiki/Second_messenger_systemhttp://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttp://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttp://en.wikipedia.org/wiki/Membrane_potentialhttp://en.wikipedia.org/wiki/Stretch-activated_ion_channelhttp://en.wikipedia.org/wiki/Stretch-activated_ion_channelhttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-Purves-1http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid15157178-28/3/2019 Excitatory Synapse
12/15
Contents
[hide]
1 Regulation
2 Structure 3 Example: nicotinic acetylcholine receptor
4 Classification
o 4.1 Cys-loop receptors
o 4.2 Ionotropic glutamate receptors
o 4.3 ATP-gated channels
5 Clinical relevance
6 See also
7 References
8 External links
[edit] Regulation
The ion channelis regulated by a ligandand is usually very selective to one or more ions like
Na+ , K+ ,Ca2+ , orCl-. Such receptors located at synapses convert the chemical signal of
presynapticallyreleased neurotransmitter directly and very quickly into apostsynapticelectricalsignal.
Many LGICs are additionally modulated by allostericligands, by channel blockers, ions, or the
membrane potential.
[edit] Structure
Each subunit of thepentamericchannels consist of the extracellular ligand-binding domain and atransmembrane domain. Each transmembrane domain in the pentamer includes four
transmembrane helixes.[4]
[edit] Example: nicotinic acetylcholine receptor
The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor. It consists of a
pentamer of protein subunits, with two binding sites foracetylcholine, which, when bound, alterthe receptor's configuration and cause an internal pore to open. This pore allowed Na+ ions to
flow down theirelectrochemical gradient into the cell. With a sufficient number of channelsopening at once, the intracellular Na+ concentration rises to the point at which the positive charge
within the cell is enough to depolarize the membrane, and an action potential is initiated.
[edit] Classification
http://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Regulationhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Structurehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Example:_nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Classificationhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Cys-loop_receptorshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Ionotropic_glutamate_receptorshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#ATP-gated_channelshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Clinical_relevancehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#See_alsohttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Referenceshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#External_linkshttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=1http://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Chloridehttp://en.wikipedia.org/wiki/Chloridehttp://en.wikipedia.org/wiki/Chloridehttp://en.wikipedia.org/wiki/Synapsehttp://en.wikipedia.org/wiki/Presynaptichttp://en.wikipedia.org/wiki/Presynaptichttp://en.wikipedia.org/wiki/Postsynaptichttp://en.wikipedia.org/wiki/Postsynaptichttp://en.wikipedia.org/wiki/Allosterichttp://en.wikipedia.org/wiki/Allosterichttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Channel_blockershttp://en.wikipedia.org/wiki/Ionhttp://en.wikipedia.org/wiki/Membrane_potentialhttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=2http://en.wikipedia.org/wiki/Pentamerhttp://en.wikipedia.org/wiki/Pentamerhttp://en.wikipedia.org/wiki/Transmembrane_helixhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid15023997-3http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=3http://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Acetylcholinehttp://en.wikipedia.org/wiki/Electrochemical_gradienthttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=4http://en.wikipedia.org/wiki/Ligand-gated_ion_channelhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Regulationhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Structurehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Example:_nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Classificationhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Cys-loop_receptorshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Ionotropic_glutamate_receptorshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#ATP-gated_channelshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Clinical_relevancehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#See_alsohttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#Referenceshttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#External_linkshttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=1http://en.wikipedia.org/wiki/Ion_channelhttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Potassiumhttp://en.wikipedia.org/wiki/Calciumhttp://en.wikipedia.org/wiki/Chloridehttp://en.wikipedia.org/wiki/Synapsehttp://en.wikipedia.org/wiki/Presynaptichttp://en.wikipedia.org/wiki/Postsynaptichttp://en.wikipedia.org/wiki/Allosterichttp://en.wikipedia.org/wiki/Ligand_(biochemistry)http://en.wikipedia.org/wiki/Channel_blockershttp://en.wikipedia.org/wiki/Ionhttp://en.wikipedia.org/wiki/Membrane_potentialhttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=2http://en.wikipedia.org/wiki/Pentamerhttp://en.wikipedia.org/wiki/Transmembrane_helixhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid15023997-3http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=3http://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Acetylcholinehttp://en.wikipedia.org/wiki/Electrochemical_gradienthttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Action_potentialhttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=48/3/2019 Excitatory Synapse
13/15
Many important ion channels are ligand-gated, and they show a significant degree ofhomology
at the genetic level. LGICs are classified into three superfamilies:
[edit] Cys-loop receptors
The cys-loop receptors contain a characteristic loop formed by a disulfide bond between twocysteineresidues and are subdivided into the type of ion that the corresponding channel conducts(anionic or cationic) and further into families defined by the endogenous ligand. They are usually
pentameric.
Vertebrate Anionic Cys-loop Receptors
Type ClassIUPHAR-recommended
protein name[5]Gene Previous names
GABAA
alpha
12
3456
GABRA1
GABRA2
GABRA3GABRA4
GABRA5GABRA6
EJM, ECA4
beta123
GABRB1
GABRB2
GABRB3 ECA5
gamma123
GABRG1
GABRG2
GABRG3
CAE2, ECA2, GEFSP3
delta GABRD
epsilon GABRE
pi GABRP
theta GABRQ
rho
123
GABRR1
GABRR2
GABRR3GABAC
[6]
Glycine
(GlyR)
alpha
1234
GLRA1GLRA2
GLRA3
GLRA4
STHE
beta GLRB
Vertebrate Cationic Cys-loop Receptors
Type Class
IUPHAR-
recommended
protein name [5]Gene Previous names
Serotonin 5-HT3 5-HT3A HTR3A 5-HT3A
http://en.wikipedia.org/wiki/Homology_(biology)http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=5http://en.wikipedia.org/wiki/Cys-loop_receptorshttp://en.wikipedia.org/wiki/Cysteinehttp://en.wikipedia.org/wiki/Cysteinehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/GABAA_receptorhttp://en.wikipedia.org/wiki/GABRA1http://en.wikipedia.org/wiki/GABRA1http://en.wikipedia.org/wiki/GABRA2http://en.wikipedia.org/wiki/GABRA2http://en.wikipedia.org/wiki/GABRA3http://en.wikipedia.org/wiki/GABRA3http://en.wikipedia.org/wiki/GABRA4http://en.wikipedia.org/wiki/GABRA4http://en.wikipedia.org/wiki/GABRA5http://en.wikipedia.org/wiki/GABRA5http://en.wikipedia.org/wiki/GABRA6http://en.wikipedia.org/wiki/GABRA6http://www.genenames.org/data/hgnc_data.php?match=GABRA1http://www.genenames.org/data/hgnc_data.php?match=GABRA2http://www.genenames.org/data/hgnc_data.php?match=GABRA3http://www.genenames.org/data/hgnc_data.php?match=GABRA4http://www.genenames.org/data/hgnc_data.php?match=GABRA5http://www.genenames.org/data/hgnc_data.php?match=GABRA6http://en.wikipedia.org/wiki/GABRB1http://en.wikipedia.org/wiki/GABRB1http://en.wikipedia.org/wiki/GABRB2http://en.wikipedia.org/wiki/GABRB2http://en.wikipedia.org/wiki/GABRB3http://en.wikipedia.org/wiki/GABRB3http://www.genenames.org/data/hgnc_data.php?match=GABRB1http://www.genenames.org/data/hgnc_data.php?match=GABRB2http://www.genenames.org/data/hgnc_data.php?match=GABRB3http://en.wikipedia.org/wiki/GABRG1http://en.wikipedia.org/wiki/GABRG1http://en.wikipedia.org/wiki/GABRG2http://en.wikipedia.org/wiki/GABRG2http://en.wikipedia.org/wiki/GABRG3http://en.wikipedia.org/wiki/GABRG3http://www.genenames.org/data/hgnc_data.php?match=GABRG1http://www.genenames.org/data/hgnc_data.php?match=GABRG2http://www.genenames.org/data/hgnc_data.php?match=GABRG3http://en.wikipedia.org/wiki/GABRDhttp://www.genenames.org/data/hgnc_data.php?match=GABRDhttp://en.wikipedia.org/wiki/GABREhttp://www.genenames.org/data/hgnc_data.php?match=GABREhttp://en.wikipedia.org/wiki/GABRPhttp://www.genenames.org/data/hgnc_data.php?match=GABRPhttp://en.wikipedia.org/wiki/GABRQhttp://www.genenames.org/data/hgnc_data.php?match=GABRQhttp://en.wikipedia.org/wiki/GABRR1http://en.wikipedia.org/wiki/GABRR1http://en.wikipedia.org/wiki/GABRR2http://en.wikipedia.org/wiki/GABRR2http://en.wikipedia.org/wiki/GABRR3http://en.wikipedia.org/wiki/GABRR3http://www.genenames.org/data/hgnc_data.php?match=GABRR1http://www.genenames.org/data/hgnc_data.php?match=GABRR2http://www.genenames.org/data/hgnc_data.php?match=GABRR3http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid18790874-5http://en.wikipedia.org/wiki/Glycine_receptorhttp://en.wikipedia.org/wiki/GLRA1http://en.wikipedia.org/wiki/GLRA1http://en.wikipedia.org/wiki/GLRA2http://en.wikipedia.org/wiki/GLRA2http://en.wikipedia.org/wiki/GLRA3http://en.wikipedia.org/wiki/GLRA3http://en.wikipedia.org/wiki/GLRA4http://en.wikipedia.org/wiki/GLRA4http://www.genenames.org/data/hgnc_data.php?match=GLRA1http://www.genenames.org/data/hgnc_data.php?match=GLRA2http://www.genenames.org/data/hgnc_data.php?match=GLRA3http://www.genenames.org/data/hgnc_data.php?match=GLRA4http://en.wikipedia.org/wiki/GLRBhttp://www.genenames.org/data/hgnc_data.php?match=GLRBhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/Serotonin_receptorhttp://en.wikipedia.org/wiki/5-HT3_receptorhttp://en.wikipedia.org/wiki/5-HT3_receptorhttp://en.wikipedia.org/wiki/HTR3Ahttp://www.genenames.org/data/hgnc_data.php?match=HTR3Ahttp://en.wikipedia.org/wiki/Homology_(biology)http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=5http://en.wikipedia.org/wiki/Cys-loop_receptorshttp://en.wikipedia.org/wiki/Cysteinehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/GABAA_receptorhttp://en.wikipedia.org/wiki/GABRA1http://en.wikipedia.org/wiki/GABRA2http://en.wikipedia.org/wiki/GABRA3http://en.wikipedia.org/wiki/GABRA4http://en.wikipedia.org/wiki/GABRA5http://en.wikipedia.org/wiki/GABRA6http://www.genenames.org/data/hgnc_data.php?match=GABRA1http://www.genenames.org/data/hgnc_data.php?match=GABRA2http://www.genenames.org/data/hgnc_data.php?match=GABRA3http://www.genenames.org/data/hgnc_data.php?match=GABRA4http://www.genenames.org/data/hgnc_data.php?match=GABRA5http://www.genenames.org/data/hgnc_data.php?match=GABRA6http://en.wikipedia.org/wiki/GABRB1http://en.wikipedia.org/wiki/GABRB2http://en.wikipedia.org/wiki/GABRB3http://www.genenames.org/data/hgnc_data.php?match=GABRB1http://www.genenames.org/data/hgnc_data.php?match=GABRB2http://www.genenames.org/data/hgnc_data.php?match=GABRB3http://en.wikipedia.org/wiki/GABRG1http://en.wikipedia.org/wiki/GABRG2http://en.wikipedia.org/wiki/GABRG3http://www.genenames.org/data/hgnc_data.php?match=GABRG1http://www.genenames.org/data/hgnc_data.php?match=GABRG2http://www.genenames.org/data/hgnc_data.php?match=GABRG3http://en.wikipedia.org/wiki/GABRDhttp://www.genenames.org/data/hgnc_data.php?match=GABRDhttp://en.wikipedia.org/wiki/GABREhttp://www.genenames.org/data/hgnc_data.php?match=GABREhttp://en.wikipedia.org/wiki/GABRPhttp://www.genenames.org/data/hgnc_data.php?match=GABRPhttp://en.wikipedia.org/wiki/GABRQhttp://www.genenames.org/data/hgnc_data.php?match=GABRQhttp://en.wikipedia.org/wiki/GABRR1http://en.wikipedia.org/wiki/GABRR2http://en.wikipedia.org/wiki/GABRR3http://www.genenames.org/data/hgnc_data.php?match=GABRR1http://www.genenames.org/data/hgnc_data.php?match=GABRR2http://www.genenames.org/data/hgnc_data.php?match=GABRR3http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid18790874-5http://en.wikipedia.org/wiki/Glycine_receptorhttp://en.wikipedia.org/wiki/GLRA1http://en.wikipedia.org/wiki/GLRA2http://en.wikipedia.org/wiki/GLRA3http://en.wikipedia.org/wiki/GLRA4http://www.genenames.org/data/hgnc_data.php?match=GLRA1http://www.genenames.org/data/hgnc_data.php?match=GLRA2http://www.genenames.org/data/hgnc_data.php?match=GLRA3http://www.genenames.org/data/hgnc_data.php?match=GLRA4http://en.wikipedia.org/wiki/GLRBhttp://www.genenames.org/data/hgnc_data.php?match=GLRBhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/Serotonin_receptorhttp://en.wikipedia.org/wiki/5-HT3_receptorhttp://en.wikipedia.org/wiki/HTR3Ahttp://www.genenames.org/data/hgnc_data.php?match=HTR3A8/3/2019 Excitatory Synapse
14/15
(5-HT)
5-HT3B
5-HT3C
5-HT3D5-HT3E
HTR3BHTR3C
HTR3D
HTR3E
5-HT3B5-HT3C5-HT3D5-HT3E
Nicotinicacetylcholine
(nAChR)
alpha
1
234567910
CHRNA1
CHRNA2CHRNA3
CHRNA4CHRNA5
CHRNA6
CHRNA7CHRNA9
CHRNA10
ACHRA, ACHRD, CHRNA,
CMS2A, FCCMS, SCCMS
beta
123
4
CHRNB1
CHRNB2CHRNB3
CHRNB4
CMS2A, SCCMS, ACHRB,
CHRNB, CMS1DEFNL3, nAChRB2
gamma CHRNG ACHRG
delta CHRNDACHRD, CMS2A, FCCMS,
SCCMS
epsilon CHRNEACHRE, CMS1D, CMS1E,
CMS2A, FCCMS, SCCMS
Zinc-activated ionchannel
(ZAC)
ZAC ZACN ZAC1, L2m LGICZ, LGICZ1
[edit] Ionotropic glutamate receptors
The ionotropic glutamate receptorsbind the neurotransmitterglutamate. They form tetramers.
Type Class
IUPHAR-
recommended
protein name[5]Gene Previous names
AMPA GluA
GluA1
GluA2
GluA3
GluA4
GRIA1GRIA2
GRIA3
GRIA4
GLUA1, GluR1, GluRA, GluR-A, GluR-K1,
HBGR1
GLUA2, GluR2, GluRB, GluR-B, GluR-K2,
HBGR2
GLUA3, GluR3, GluRC, GluR-C, GluR-K3GLUA4, GluR4, GluRD, GluR-D
Kainate GluK
GluK1GluK2
GluK3
GluK4GluK5
GRIK1
GRIK2
GRIK3GRIK4
GRIK5
GLUK5, GluR5, GluR-5, EAA3GLUK6, GluR6, GluR-6, EAA4
GLUK7, GluR7, GluR-7, EAA5
GLUK1, KA1, KA-1, EAA1GLUK2, KA2, KA-2, EAA2
NMDA GluN GluN1 GRIN1 GLUN1, NMDA-R1, NR1, GluR1
http://en.wikipedia.org/wiki/HTR3Bhttp://en.wikipedia.org/wiki/HTR3Chttp://en.wikipedia.org/wiki/HTR3Dhttp://en.wikipedia.org/wiki/HTR3Ehttp://www.genenames.org/data/hgnc_data.php?match=HTR3Bhttp://www.genenames.org/data/hgnc_data.php?match=HTR3Chttp://www.genenames.org/data/hgnc_data.php?match=HTR3Dhttp://www.genenames.org/data/hgnc_data.php?match=HTR3Ehttp://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/CHRNA1http://en.wikipedia.org/wiki/CHRNA1http://en.wikipedia.org/wiki/CHRNA2http://en.wikipedia.org/wiki/CHRNA2http://en.wikipedia.org/wiki/CHRNA3http://en.wikipedia.org/wiki/CHRNA3http://en.wikipedia.org/wiki/CHRNA4http://en.wikipedia.org/wiki/CHRNA4http://en.wikipedia.org/wiki/CHRNA5http://en.wikipedia.org/wiki/CHRNA5http://en.wikipedia.org/wiki/CHRNA6http://en.wikipedia.org/wiki/CHRNA6http://en.wikipedia.org/wiki/CHRNA7http://en.wikipedia.org/wiki/CHRNA7http://en.wikipedia.org/wiki/CHRNA9http://en.wikipedia.org/wiki/CHRNA9http://en.wikipedia.org/wiki/CHRNA10http://en.wikipedia.org/wiki/CHRNA10http://www.genenames.org/data/hgnc_data.php?match=CHRNA1http://www.genenames.org/data/hgnc_data.php?match=CHRNA2http://www.genenames.org/data/hgnc_data.php?match=CHRNA3http://www.genenames.org/data/hgnc_data.php?match=CHRNA4http://www.genenames.org/data/hgnc_data.php?match=CHRNA5http://www.genenames.org/data/hgnc_data.php?match=CHRNA6http://www.genenames.org/data/hgnc_data.php?match=CHRNA7http://www.genenames.org/data/hgnc_data.php?match=CHRNA9http://www.genenames.org/data/hgnc_data.php?match=CHRNA10http://en.wikipedia.org/wiki/CHRNB1http://en.wikipedia.org/wiki/CHRNB1http://en.wikipedia.org/wiki/CHRNB2http://en.wikipedia.org/wiki/CHRNB2http://en.wikipedia.org/wiki/CHRNB3http://en.wikipedia.org/wiki/CHRNB3http://en.wikipedia.org/wiki/CHRNB4http://en.wikipedia.org/wiki/CHRNB4http://www.genenames.org/data/hgnc_data.php?match=CHRNB1http://www.genenames.org/data/hgnc_data.php?match=CHRNB2http://www.genenames.org/data/hgnc_data.php?match=CHRNB3http://www.genenames.org/data/hgnc_data.php?match=CHRNB4http://en.wikipedia.org/wiki/CHRNGhttp://www.genenames.org/data/hgnc_data.php?match=CHRNGhttp://en.wikipedia.org/wiki/CHRNDhttp://www.genenames.org/data/hgnc_data.php?match=CHRNDhttp://en.wikipedia.org/wiki/CHRNEhttp://www.genenames.org/data/hgnc_data.php?match=CHRNEhttp://en.wikipedia.org/wiki/Zinc-activated_ion_channelhttp://en.wikipedia.org/wiki/Zinc-activated_ion_channelhttp://www.genenames.org/data/hgnc_data.php?match=ZACNhttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=6http://en.wikipedia.org/wiki/Ionotropic_glutamate_receptorhttp://en.wikipedia.org/wiki/Ionotropic_glutamate_receptorhttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Glutamic_acidhttp://en.wikipedia.org/wiki/Glutamic_acidhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/AMPA_receptorhttp://en.wikipedia.org/wiki/GRIA1http://en.wikipedia.org/wiki/GRIA2http://en.wikipedia.org/wiki/GRIA3http://en.wikipedia.org/wiki/GRIA4http://www.genenames.org/data/hgnc_data.php?match=GRIA1http://www.genenames.org/data/hgnc_data.php?match=GRIA2http://www.genenames.org/data/hgnc_data.php?match=GRIA3http://www.genenames.org/data/hgnc_data.php?match=GRIA4http://en.wikipedia.org/wiki/Kainate_receptorhttp://en.wikipedia.org/wiki/GRIK1http://en.wikipedia.org/wiki/GRIK2http://en.wikipedia.org/wiki/GRIK3http://en.wikipedia.org/wiki/GRIK4http://en.wikipedia.org/wiki/GRIK5http://www.genenames.org/data/hgnc_data.php?match=GRIK1http://www.genenames.org/data/hgnc_data.php?match=GRIK2http://www.genenames.org/data/hgnc_data.php?match=GRIK3http://www.genenames.org/data/hgnc_data.php?match=GRIK4http://www.genenames.org/data/hgnc_data.php?match=GRIK5http://en.wikipedia.org/wiki/NMDA_receptorhttp://en.wikipedia.org/wiki/GRIN1http://www.genenames.org/data/hgnc_data.php?match=GRIN1http://en.wikipedia.org/wiki/HTR3Bhttp://en.wikipedia.org/wiki/HTR3Chttp://en.wikipedia.org/wiki/HTR3Dhttp://en.wikipedia.org/wiki/HTR3Ehttp://www.genenames.org/data/hgnc_data.php?match=HTR3Bhttp://www.genenames.org/data/hgnc_data.php?match=HTR3Chttp://www.genenames.org/data/hgnc_data.php?match=HTR3Dhttp://www.genenames.org/data/hgnc_data.php?match=HTR3Ehttp://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/CHRNA1http://en.wikipedia.org/wiki/CHRNA2http://en.wikipedia.org/wiki/CHRNA3http://en.wikipedia.org/wiki/CHRNA4http://en.wikipedia.org/wiki/CHRNA5http://en.wikipedia.org/wiki/CHRNA6http://en.wikipedia.org/wiki/CHRNA7http://en.wikipedia.org/wiki/CHRNA9http://en.wikipedia.org/wiki/CHRNA10http://www.genenames.org/data/hgnc_data.php?match=CHRNA1http://www.genenames.org/data/hgnc_data.php?match=CHRNA2http://www.genenames.org/data/hgnc_data.php?match=CHRNA3http://www.genenames.org/data/hgnc_data.php?match=CHRNA4http://www.genenames.org/data/hgnc_data.php?match=CHRNA5http://www.genenames.org/data/hgnc_data.php?match=CHRNA6http://www.genenames.org/data/hgnc_data.php?match=CHRNA7http://www.genenames.org/data/hgnc_data.php?match=CHRNA9http://www.genenames.org/data/hgnc_data.php?match=CHRNA10http://en.wikipedia.org/wiki/CHRNB1http://en.wikipedia.org/wiki/CHRNB2http://en.wikipedia.org/wiki/CHRNB3http://en.wikipedia.org/wiki/CHRNB4http://www.genenames.org/data/hgnc_data.php?match=CHRNB1http://www.genenames.org/data/hgnc_data.php?match=CHRNB2http://www.genenames.org/data/hgnc_data.php?match=CHRNB3http://www.genenames.org/data/hgnc_data.php?match=CHRNB4http://en.wikipedia.org/wiki/CHRNGhttp://www.genenames.org/data/hgnc_data.php?match=CHRNGhttp://en.wikipedia.org/wiki/CHRNDhttp://www.genenames.org/data/hgnc_data.php?match=CHRNDhttp://en.wikipedia.org/wiki/CHRNEhttp://www.genenames.org/data/hgnc_data.php?match=CHRNEhttp://en.wikipedia.org/wiki/Zinc-activated_ion_channelhttp://en.wikipedia.org/wiki/Zinc-activated_ion_channelhttp://www.genenames.org/data/hgnc_data.php?match=ZACNhttp://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=6http://en.wikipedia.org/wiki/Ionotropic_glutamate_receptorhttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Glutamic_acidhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/AMPA_receptorhttp://en.wikipedia.org/wiki/GRIA1http://en.wikipedia.org/wiki/GRIA2http://en.wikipedia.org/wiki/GRIA3http://en.wikipedia.org/wiki/GRIA4http://www.genenames.org/data/hgnc_data.php?match=GRIA1http://www.genenames.org/data/hgnc_data.php?match=GRIA2http://www.genenames.org/data/hgnc_data.php?match=GRIA3http://www.genenames.org/data/hgnc_data.php?match=GRIA4http://en.wikipedia.org/wiki/Kainate_receptorhttp://en.wikipedia.org/wiki/GRIK1http://en.wikipedia.org/wiki/GRIK2http://en.wikipedia.org/wiki/GRIK3http://en.wikipedia.org/wiki/GRIK4http://en.wikipedia.org/wiki/GRIK5http://www.genenames.org/data/hgnc_data.php?match=GRIK1http://www.genenames.org/data/hgnc_data.php?match=GRIK2http://www.genenames.org/data/hgnc_data.php?match=GRIK3http://www.genenames.org/data/hgnc_data.php?match=GRIK4http://www.genenames.org/data/hgnc_data.php?match=GRIK5http://en.wikipedia.org/wiki/NMDA_receptorhttp://en.wikipedia.org/wiki/GRIN1http://www.genenames.org/data/hgnc_data.php?match=GRIN18/3/2019 Excitatory Synapse
15/15
NRL1A
NRL1B
GRINL1AGRINL1B
G luN2A
GluN2B
GluN2C
GluN2D
GRIN2A
GRIN2BGRIN2C
GRIN2D
GLUN2A, NMDA-R2A, NR2A, GluR1GLUN2B, NMDA-R2B, NR2B, hNR3,
GluR2
GLUN2C, NMDA-R2C, NR2C, GluR3GLUN2D, NMDA-R2D, NR2D, GluR4
GluN3A
GluN3B
GRIN3AGRIN3B
GLUN3A, NMDA-R3A, NMDAR-L, chi-1
GLU3B, NMDA-R3B
Orphan (GluD)
GluD1GluD2
GRID1
GRID2GluR1GluR2
[edit] ATP-gated channels
Main article: P2X receptor
ATP-gated channels open in response to binding the nucleotideATP. They form trimers.
Type ClassIUPHAR-recommended
protein name [5]Gene Previous names
P2X N/A
P2X1
P2X2
P2X3
P2X4P2X5
P2X6
P2X7
P2RX1
P2RX2P2RX3
P2RX4
P2RX5
P2RX6P2RX7
P2X1P2X2P2X3P2X4P2X5P2X6P2X7
[edit] Clinical relevance
Ligand-gated ion channels are likely to be the major site at whichanaesthetic agents and ethanol
have their effects, although unequivocal evidence of this is yet to be established.[7][8] In particular,
the GABA andNMDA receptors are affected by anaestheticagents at concentrations similar tothose used in clinical anaesthesia.[9]
http://en.wikipedia.org/wiki/GRINL1Ahttp://en.wikipedia.org/wiki/GRINL1Bhttp://www.genenames.org/data/hgnc_data.php?match=GRINL1Ahttp://www.genenames.org/data/hgnc_data.php?match=GRINL1Bhttp://en.wikipedia.org/wiki/GRIN2Ahttp://en.wikipedia.org/wiki/GRIN2Bhttp://en.wikipedia.org/wiki/GRIN2Chttp://en.wikipedia.org/wiki/GRIN2Dhttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Ahttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Bhttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Chttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Dhttp://en.wikipedia.org/wiki/GRIN2Ahttp://en.wikipedia.org/wiki/GRIN3Bhttp://www.genenames.org/data/hgnc_data.php?match=GRIN3Ahttp://www.genenames.org/data/hgnc_data.php?match=GRIN3Bhttp://en.wikipedia.org/wiki/GRID1http://en.wikipedia.org/wiki/GRID2http://www.genenames.org/data/hgnc_data.php?match=GRID1http://www.genenames.org/data/hgnc_data.php?match=GRID2http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=7http://en.wikipedia.org/wiki/P2X_receptorhttp://en.wikipedia.org/wiki/Nucleotidehttp://en.wikipedia.org/wiki/Adenosine_triphosphatehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/P2X_Receptorhttp://en.wikipedia.org/wiki/P2RX1http://en.wikipedia.org/wiki/P2RX2http://en.wikipedia.org/wiki/P2RX3http://en.wikipedia.org/wiki/P2RX4http://en.wikipedia.org/wiki/P2RX5http://en.wikipedia.org/wiki/P2RX6http://en.wikipedia.org/wiki/P2RX7http://www.genenames.org/data/hgnc_data.php?match=P2RX1http://www.genenames.org/data/hgnc_data.php?match=P2RX2http://www.genenames.org/data/hgnc_data.php?match=P2RX3http://www.genenames.org/data/hgnc_data.php?match=P2RX4http://www.genenames.org/data/hgnc_data.php?match=P2RX5http://www.genenames.org/data/hgnc_data.php?match=P2RX6http://www.genenames.org/data/hgnc_data.php?match=P2RX7http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=8http://en.wikipedia.org/wiki/Anaesthetichttp://en.wikipedia.org/wiki/Anaesthetichttp://en.wikipedia.org/wiki/Ethanolhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid10487207-6http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid12173240-7http://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/NMDAhttp://en.wikipedia.org/wiki/Anaesthetichttp://en.wikipedia.org/wiki/Anaesthetichttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid7589987-8http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid7589987-8http://en.wikipedia.org/wiki/GRINL1Ahttp://en.wikipedia.org/wiki/GRINL1Bhttp://www.genenames.org/data/hgnc_data.php?match=GRINL1Ahttp://www.genenames.org/data/hgnc_data.php?match=GRINL1Bhttp://en.wikipedia.org/wiki/GRIN2Ahttp://en.wikipedia.org/wiki/GRIN2Bhttp://en.wikipedia.org/wiki/GRIN2Chttp://en.wikipedia.org/wiki/GRIN2Dhttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Ahttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Bhttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Chttp://www.genenames.org/data/hgnc_data.php?match=GRIN2Dhttp://en.wikipedia.org/wiki/GRIN2Ahttp://en.wikipedia.org/wiki/GRIN3Bhttp://www.genenames.org/data/hgnc_data.php?match=GRIN3Ahttp://www.genenames.org/data/hgnc_data.php?match=GRIN3Bhttp://en.wikipedia.org/wiki/GRID1http://en.wikipedia.org/wiki/GRID2http://www.genenames.org/data/hgnc_data.php?match=GRID1http://www.genenames.org/data/hgnc_data.php?match=GRID2http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=7http://en.wikipedia.org/wiki/P2X_receptorhttp://en.wikipedia.org/wiki/Nucleotidehttp://en.wikipedia.org/wiki/Adenosine_triphosphatehttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-IUPHAR-4http://en.wikipedia.org/wiki/P2X_Receptorhttp://en.wikipedia.org/wiki/P2RX1http://en.wikipedia.org/wiki/P2RX2http://en.wikipedia.org/wiki/P2RX3http://en.wikipedia.org/wiki/P2RX4http://en.wikipedia.org/wiki/P2RX5http://en.wikipedia.org/wiki/P2RX6http://en.wikipedia.org/wiki/P2RX7http://www.genenames.org/data/hgnc_data.php?match=P2RX1http://www.genenames.org/data/hgnc_data.php?match=P2RX2http://www.genenames.org/data/hgnc_data.php?match=P2RX3http://www.genenames.org/data/hgnc_data.php?match=P2RX4http://www.genenames.org/data/hgnc_data.php?match=P2RX5http://www.genenames.org/data/hgnc_data.php?match=P2RX6http://www.genenames.org/data/hgnc_data.php?match=P2RX7http://en.wikipedia.org/w/index.php?title=Ligand-gated_ion_channel&action=edit§ion=8http://en.wikipedia.org/wiki/Anaesthetichttp://en.wikipedia.org/wiki/Ethanolhttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid10487207-6http://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid12173240-7http://en.wikipedia.org/wiki/GABAhttp://en.wikipedia.org/wiki/NMDAhttp://en.wikipedia.org/wiki/Anaesthetichttp://en.wikipedia.org/wiki/Ligand-gated_ion_channel#cite_note-pmid7589987-8