H.Gaub / SS 2007BPZ§4.11 Biophysics of excitable cells.

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H.Gaub / SS 2007 BPZ§4.1 1

Biophysics of excitable cells

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Axons are specialized for the conduction of an electrical impulse called an action potential

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Specialized regions of neurons carry out different functions

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Experimental techniques are conceptually simple

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Cell-Semiconductor-Hybrids: Neuron on the Chip

More: Fromherz MPI Martinsried

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Cell-Semiconductor-Hybrids: Neuron on the Chip

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Synapses are specialized sites where neurons communicate with other cells

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Multiple exitatory and inhibitory synaptic contacts allow complex neuronal interconnects

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Neurons are organized into circuits

The knee-jerk reflex arc in the human.

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A schematic of the vertebrate nervous system

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Membrane depolarizations spread passively only short distances

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The electrical activity of neurons results from the opening and closing of specific ion-channels proteins in the neuron plasma membrane

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Voltage-gated cation channels generate action potentials

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The structure and function of the voltage-gated Na+ channel

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Action potentials are propagated unidirectionally without diminution

Movements of onlya few Na+ and K+

ions generate theaction potential

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Myelination increases the velocity of impulse conduction

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Formation and structure of a myelin sheath in the peripheral nervous system

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Each region of myelin formed by an individual glial cell is separated from the next region by an unmyelinated area called the node of Ranvier

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Action potentials travel rapidly from one node to the next

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Patch clamps permit measurement of ion movements through single channels

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Different patch clamping configurations

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Current flux through individual voltage-gated channels determined by patch clamping of muscle cells

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The oocyte expression assay can be used to determine if a protein is an ion channel

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Voltage-gated K+ channels have four subunits each containing six transmembrane helices

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All five subunits in the nicotinic acetylcholine receptor contribute to the ion channel

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P segments form the ion-selectivity filter

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All pore-forming ion channels are similar in structure

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Acetylcholine and other transmitters can activate multiple receptors

Acetylcholine is released by motor neurons at neuromuscular junctions

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Neurotransmitters are small molecules that transmit impulses at chemical synapses

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Influx of Ca2+ triggers release of neurotransmitters

Synaptic vesicles can befilled, exocytosed, andrecycled within a minute

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Synaptic-vesicle and plasma-membrane proteins important for vesicle docking and fusion

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Chemical synapses can be excitatory or inhibitory

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Ligand-gated receptor ion channels function at fast synapses

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G protein-coupled receptors function at slow synapses

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Transmitter-mediated signaling is terminated by several mechanisms

• Following release of a neurotransmitter or neuropeptide, it must be removed or destroyed to prevent continued stimulation of the post-synaptic cell

• To end the signaling, the transmitter may

– diffuse away from the synaptic cleft

– be taken up by the pre-synaptic neuron

– be enzymatically degraded

• Signaling by acetylcholine and neuropeptides is terminated by enzymatic degradation

• Signaling by most classic neurotransmitters is terminated by uptake

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Impulses transmitted across chemical synapses can be amplified and computed

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Opening of acetylcholine-gated cation channels leads to muscle contraction

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Cardiac muscarinic acetylcholine receptors activate a G protein that opens an ion channel

Catecholamine receptors also induce changes in second-messenger levels that affect ion-channel activity

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A serotonin receptor indirectly modulates K+ channel function by activating adenylate cyclase

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Membrane disks in the outer segments of rod cells contain rhodopsin, a light-sensitive protein

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Absorption of a photon triggers isomerization of retinal and activation of opsin

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Cyclic GMP is a key transducing molecule in rod cells

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A thousand different G protein-coupled receptors detect odors

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Impulse transmission across electric synapses is nearly instantaneous

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Comparison of action potential transmission across electric and chemical synapses

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Learning and memory

• Learning is the process by which animals modify their behavior as a result of experience or acquisition of information about the environment

• Memory is the process by which this information is stored and retrieved

– Long term memory involves the formation or elimination of certain synapses

– Short-term memory involves changes in the release and function of neurotransmitters at specific synapses

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Study of the gill withdrawal reflex of Aplysia has provided insight into short-term learning processes

This simple behavior exhibits the most elementary forms of learning familiar in vertebrates: habituation, sensitization, and classical conditioning

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Facilitator neurons mediate sensitization of Aplysia withdrawal reflex

Individuals were restrained in small aquariums in a manner that the gill was exposed. A tactile stimulus was administered to the siphon and elicited the gill and siphon withdrawal reflex. A photocell was placed under the gill to record amplitude and duration of the response elicited by the stimulus.Habituation was observed when the stimulus was delivered repeatedly to the siphon. Stimulus every 90 seconds resulted in a rapidly declined response. By delivering an electric shock to the tail the response was rapidly restored, dishabituation occurred. Sensitization was observed when a strong stimulus was administered to the tail, this enhanced a completely rested reflex in Aplysia californica.

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Coincidence detectors participate in classical conditioning and sensitization