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NerveNerve

Nerve cell is neuron, 100 billion neurons Nerve cell is neuron, 100 billion neurons ±± 100 10066 differ in structure, chemistry & function. Neurons differ in structure, chemistry & function. Neurons confer unique functions of nervous system. Glia are confer unique functions of nervous system. Glia are supporting elements, 10 times as neurons. Neurons supporting elements, 10 times as neurons. Neurons contain cell body (soma or perikaryon) & neurites contain cell body (soma or perikaryon) & neurites (axons & dendrites). Cell body gives rise to single (axons & dendrites). Cell body gives rise to single axon which conducts nerve impulse from neuron to axon which conducts nerve impulse from neuron to the next, up to 1 meter length, speed of impulse is a the next, up to 1 meter length, speed of impulse is a function of diameter. Dendrites: small (rarely more function of diameter. Dendrites: small (rarely more than 2mm)& organized symmetrically (antennae). than 2mm)& organized symmetrically (antennae). Dendritic tree: all neurites. Neural signals: efferent Dendritic tree: all neurites. Neural signals: efferent (away) or afferent (towards) cell body(away) or afferent (towards) cell body..

Types of gliaTypes of gliaAstrocytesAstrocytes: Regulate EC space, remove (or restrict : Regulate EC space, remove (or restrict movement of) neurotransmittersmovement of) neurotransmitters

OligodendrocytesOligodendrocytes: Myelinating glia in CNS, form : Myelinating glia in CNS, form myelin sheath (wrap around axons, function in myelin sheath (wrap around axons, function in insulation), interruptions: nodes of Ranvierinsulation), interruptions: nodes of Ranvier..

Schwann CellsSchwann Cells:PNS, myelin sheath & neurolemma:PNS, myelin sheath & neurolemmaMicrogliaMicroglia:Scavenger cells get rid of foreign particle:Scavenger cells get rid of foreign particle

Classification of nervesClassification of nerves Physioanatomic classificationPhysioanatomic classification: afferent : afferent

(sensory) & efferent (motor), subdivided into (sensory) & efferent (motor), subdivided into somatic & visceral neurons, general & special somatic & visceral neurons, general & special neuronsneurons..

Classification according to conduction velocity and Classification according to conduction velocity and caliber of nerve fibercaliber of nerve fiber. From larger to lower caliber. From larger to lower caliber : :

AαAα largest diameter & fastest conduction velocity largest diameter & fastest conduction velocity e.g. somatic motor & proprioceptive nerve fiberse.g. somatic motor & proprioceptive nerve fibersAβAβ e.g. sensory fibers of fine touch & fine pr e.g. sensory fibers of fine touch & fine pr..AγAγ e.g. motor fibers to muscle spindle e.g. motor fibers to muscle spindle..

AδAδ e.g sensory fiber of acute pain, crude touch cold e.g sensory fiber of acute pain, crude touch coldBB e.g. preganglionic autonomic nerve fibers e.g. preganglionic autonomic nerve fibers..

CC smallest diameter unmyelinated fibers e.g. smallest diameter unmyelinated fibers e.g. sensory fibers of chronic pain, heat, gross pr. and sensory fibers of chronic pain, heat, gross pr. and

postganglionic sympathetic fiberspostganglionic sympathetic fibers . .

Resting membrane potentialResting membrane potential

All living cells (animal or plant) exhibit potential All living cells (animal or plant) exhibit potential difference across their plasma membranes when difference across their plasma membranes when microelectrodes are inserted into cells, membrane microelectrodes are inserted into cells, membrane interior is negative in relation to its exterior. This is interior is negative in relation to its exterior. This is resting membrane potential (RMP), due to uneven resting membrane potential (RMP), due to uneven distribution of ions in & outside membranedistribution of ions in & outside membrane..

Ion Extracellular Intracellular

Na+ 142 mEq/L 10 mEq/L K+ 4 mEq/L 140 mEq/L Cl– 103 mEq/L 4 mEq/L Phosphates 4 mEq/L 75 mEq/L Proteins 30 mg/dL 200 mg/dL

Accordingly, RMP of nerve cell –70 mV, Accordingly, RMP of nerve cell –70 mV, skeletal muscle s –90 mV, cardiac muscle –85 mV skeletal muscle s –90 mV, cardiac muscle –85 mV & smooth muscle is variable but nearly –50 mV& smooth muscle is variable but nearly –50 mV..

Ionic fluxes causing electric phenomenon of RMP:Ionic fluxes causing electric phenomenon of RMP:--NaNa++-K-K++ pump pump: extrude 3 Na: extrude 3 Na++ outside cell, intrude 2 outside cell, intrude 2 KK++ inside, much positive ions outside inside, much positive ions outside-NaNa++ channels are inactive channels are inactive at rest, voltage gated, at rest, voltage gated, activated by electric current activated by electric current --Passive diffusion of KPassive diffusion of K++ outside outside, conc. gradient, , conc. gradient, diffusion potential, major factor of RMP diffusion potential, major factor of RMP --ClCl-- ions still inside ions still inside, due to higher conc. outside , due to higher conc. outside --Anionic proteins & phosphates stay inside,Anionic proteins & phosphates stay inside, large large size, PM impermeablesize, PM impermeable

-

PROTEINS¯ PHOSPHATES¯ CHLORIDE¯ 2K+

3Na+

K+

Pump

Action potential Action potential

Nerve and muscle cells are excitable cells, have the Nerve and muscle cells are excitable cells, have the ability to reverse the negativity of their membrane ability to reverse the negativity of their membrane potential in response to a sufficient external potential in response to a sufficient external stimulus. The external stimulus may be electrical, stimulus. The external stimulus may be electrical, chemical, physical or other types of stimuli. This chemical, physical or other types of stimuli. This change in membrane potential is action potential. change in membrane potential is action potential. Response in nerve cell is transmission of nerve Response in nerve cell is transmission of nerve impulse while response in muscle cell is contractionimpulse while response in muscle cell is contraction

Cathodal stimuli, Cathodal stimuli, local responseslocal responses, increase & , increase & decrease with amplitudes of stimuli, subside after decrease with amplitudes of stimuli, subside after removal of these stimuli. Sufficient stimulus raises removal of these stimuli. Sufficient stimulus raises the membrane potential 15 mV above RMP (i.e. –the membrane potential 15 mV above RMP (i.e. –55 mV); AP phases will start & does not stop until 55 mV); AP phases will start & does not stop until complete cycle occurs, complete cycle occurs, all-or-noneall-or-none rule. Membrane rule. Membrane potential at which AP starts is potential at which AP starts is threshold or firing threshold or firing potentialpotential. . SubthresholdSubthreshold stimuli no or local effects, stimuli no or local effects, supramaximalsupramaximal stimuli the same effects as threshold stimuli the same effects as threshold

Phases of AP in neurons:Phases of AP in neurons:Depolarization phaseDepolarization phase: Sharp rise, 0 potential, : Sharp rise, 0 potential, overshootsovershoots,about +35 mV (activate all Na,about +35 mV (activate all Na++channels, channels, inrush of huge number of Nainrush of huge number of Na++, PM lose negativity, PM lose negativityRepolarization phaseRepolarization phase: Rapid fall toward negative : Rapid fall toward negative potential (inactivate Napotential (inactivate Na++ channels, continuous channels, continuous pumping of Napumping of Na++ & passive diffusion of K & passive diffusion of K++ outside) outside)Hyperpolarization phaseHyperpolarization phase: Decline more negative : Decline more negative potential than RMP,–72 mV (slow closure of Kpotential than RMP,–72 mV (slow closure of K++ channels, after that, RMP again)channels, after that, RMP again)

Any stimulus does not induce new AP at time of Any stimulus does not induce new AP at time of previous depolarization until third repolarization previous depolarization until third repolarization ((absolute refractory periodabsolute refractory period: Na: Na++ channels cannot channels cannot reactivated immediately after previous activation). reactivated immediately after previous activation). From third repolarization to end of repolarization From third repolarization to end of repolarization phase, stronger stimulus induces new, but weaker phase, stronger stimulus induces new, but weaker AP (AP (relative refractory periodrelative refractory period: fewer Na: fewer Na++ channels channels can be activated). Cacan be activated). Ca2+2+stabilize membrane, increase stabilize membrane, increase threshold potential threshold potential ﴾﴾more positivemore positive﴿﴿. Lack of Ca. Lack of Ca2+2+: : lower threshold potential, membrane very excitable lower threshold potential, membrane very excitable , continuously firing , continuously firing ﴾﴾tetanustetanus﴿﴿

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NerveNerve

Propagation of action potentialPropagation of action potential

AP triggered in axon hillock, presence of large No. AP triggered in axon hillock, presence of large No. of Naof Na++ channels & transmitted along axon for same channels & transmitted along axon for same reason, huge number of positive charges in firing reason, huge number of positive charges in firing segment of membrane is equilibrated by adjacent segment of membrane is equilibrated by adjacent segments, segments, electrotonic flow of currentelectrotonic flow of current, very fast , very fast type of conduction in solid wires, nerve fiber is not type of conduction in solid wires, nerve fiber is not solid wire, leaky, surrounded by sea of electrolytes, solid wire, leaky, surrounded by sea of electrolytes, continuous triggering of AP, cost time (0.1 ms each) continuous triggering of AP, cost time (0.1 ms each) , unmyelinated nerves slowest conduction velocity., unmyelinated nerves slowest conduction velocity.

Electrotonic flow of current

Myelin prevents leak, nodes of Ranvier act as Myelin prevents leak, nodes of Ranvier act as augmentation stations, strengthen wave of depolar-augmentation stations, strengthen wave of depolar-ization by triggering new AP, nodes are rich in Naization by triggering new AP, nodes are rich in Na++ channels, channels, saltatory conductionsaltatory conduction, jumping from node , jumping from node to node, one direction from soma to axon terminal to node, one direction from soma to axon terminal ((orthodromic conductionorthodromic conduction), not ), not antidromicantidromic: : absolute refractory period, proceeds forward to absolute refractory period, proceeds forward to resting segment not backward to refractory resting segment not backward to refractory segment.segment.

Synaptic and junctional transmissionSynaptic and junctional transmission

SynapseSynapse is junction between two neurons. The first is junction between two neurons. The first is is presynapticpresynaptic neuron and the other is neuron and the other is postsynapticpostsynaptic neuron. Between them is neuron. Between them is synaptic cleftsynaptic cleft..

Presynaptic N Synaptic cleft

Postsynaptic N

Synapses: Synapses: chemicalchemical or or electrical:electrical:(very rare: e.g gap (very rare: e.g gap junction, current flows directly through specialized junction, current flows directly through specialized protein molecule:connexon, distance between two protein molecule:connexon, distance between two sides of membrane is very small: 5nM). sides of membrane is very small: 5nM). Chemical:Chemical: predominant, neurotransmitters (NT) synthesized predominant, neurotransmitters (NT) synthesized & stored in vesicles, AP opens Ca& stored in vesicles, AP opens Ca2+2+ channel & Ca channel & Ca2+2+ influx, increase intracellular Cainflux, increase intracellular Ca2+2+ conc. attract conc. attract synaptic vesicles (full of NT) to presynaptic mem., synaptic vesicles (full of NT) to presynaptic mem., signals NT to release to synaptic cleft by exocytosis. signals NT to release to synaptic cleft by exocytosis.

Vesicles fuse with active zones of presynaptic mem. Vesicles fuse with active zones of presynaptic mem. NT diffuses across synaptic cleft to bind its specific NT diffuses across synaptic cleft to bind its specific receptor on postsynaptic mem. Several types of NT receptor on postsynaptic mem. Several types of NT available and each may have types & subtypes of available and each may have types & subtypes of receptors. Postsynaptic action depends on nature of receptors. Postsynaptic action depends on nature of receptor. After that, NT must be inactivated by receptor. After that, NT must be inactivated by degradation, reuptake, diffusion, or bioconversiondegradation, reuptake, diffusion, or bioconversion

Properties of synapses: Properties of synapses: 1-One-way conduction from pre- to post-synaptic 1-One-way conduction from pre- to post-synaptic neurons because post synaptic membrane contains neurons because post synaptic membrane contains no synaptic vesicles.no synaptic vesicles.2-Synapse is a site of neurotransduction (from 2-Synapse is a site of neurotransduction (from electrical to chemical signal).electrical to chemical signal).3-Intercellular chemical messages converted into 3-Intercellular chemical messages converted into intracellular signal. intracellular signal.

4-Synaptic potentials are either excitatory (4-Synaptic potentials are either excitatory (EPSPEPSP) ) or inhibitory (or inhibitory (IPSPIPSP). EPSP: depolarization: cations ). EPSP: depolarization: cations in or anions out, while IPSP: hyperpolarization:in or anions out, while IPSP: hyperpolarization:5-EPSP & IPSP present 5-EPSP & IPSP present simultaneouslysimultaneously in cleft. in cleft.6-Synaptic potentials are 6-Synaptic potentials are not all-or-nonenot all-or-none potentials. potentials. 7- 0.5 ms is 7- 0.5 ms is synaptic delaysynaptic delay8- 8- Spatiotemporal summationSpatiotemporal summation, additive or subtract-, additive or subtract-ive, numerous synaptic knobs on same neuron at ive, numerous synaptic knobs on same neuron at same time: same time: spatialspatial summation, successive impulses summation, successive impulses at same synaptic knob: at same synaptic knob: temporaltemporal summation. summation.

Spatial summation

Temporal summation

9- Several presynaptic neurons may 9- Several presynaptic neurons may convergeconverge on on single postsynaptic neuron.single postsynaptic neuron.

1-

Convergence

10-Single presynaptic neuron may 10-Single presynaptic neuron may divergediverge by its by its axon and its collaterals into several postsynaptic axon and its collaterals into several postsynaptic neurons.neurons.

Divergence

11-Axon collaterals from postsynaptic neurons may 11-Axon collaterals from postsynaptic neurons may reverberate reverberate to the presynaptic neuron(s).to the presynaptic neuron(s).

1- R everberation

12- 12- OcclusionOcclusion means that the sum of activities of means that the sum of activities of several neurons working together is less than the several neurons working together is less than the sum of their activities when they work separately. sum of their activities when they work separately.

Works separately on 2 neurons

Works separately on 2 neurons

Works separately on 2 neurons Total: separately work on 6 neurons

Total together work on 4 neurons

13- Several successive EPSP may 13- Several successive EPSP may facilitatefacilitate synaptic synaptic knob to depolarize while several successive IPSP knob to depolarize while several successive IPSP may may inhibitinhibit synaptic knob. synaptic knob.14- Continuous recurrent weak synaptic potentials 14- Continuous recurrent weak synaptic potentials may cause may cause habituationhabituation of postsynaptic neuron, not of postsynaptic neuron, not respond for similar future stimulations. Recurrent respond for similar future stimulations. Recurrent strong stimulations accompanied by other weak strong stimulations accompanied by other weak stimulations may cause stimulations may cause sensitizationsensitization

Classification of neurotransmittersClassification of neurotransmittersA. A. Small molecule, rapidly acting transmittersSmall molecule, rapidly acting transmitters:: Class I: AcetylcholineClass I: Acetylcholine Class II: The amines (adrenaline "epinephrine", Class II: The amines (adrenaline "epinephrine", noradrenaline "norepinephrine", dopamine, noradrenaline "norepinephrine", dopamine, serotonine and histamine).serotonine and histamine). Class III: Amino acids (γ-aminobutyric acid Class III: Amino acids (γ-aminobutyric acid "GABA", glycine, glutamate and aspartate)."GABA", glycine, glutamate and aspartate). Class IV: Nitric oxide "NO".Class IV: Nitric oxide "NO".

B. B. Neuropeptide, slowly acting transmittersNeuropeptide, slowly acting transmitters::a-Hypothalamic-releasing hormones.a-Hypothalamic-releasing hormones.b-Pituitary peptides.b-Pituitary peptides.c-Peptides that act on gut and brain.c-Peptides that act on gut and brain.d-Peptides from other tissues.d-Peptides from other tissues.

Criteria for classification as a NTCriteria for classification as a NT-Must be synthesized & stored in presyn. n.-Must be synthesized & stored in presyn. n.-Must be released by presyn. n. upon stimulation-Must be released by presyn. n. upon stimulation-Application of NT directly to target cell must -Application of NT directly to target cell must produce same effects as NT releaseproduce same effects as NT releaseMany neurons release more than single NT. Many neurons release more than single NT. Neurons that use acetylcholine: cholinergic, Neurons that use acetylcholine: cholinergic, catecholamines: catecholinergic, serotonine: catecholamines: catecholinergic, serotonine: serotonergic , amino acids: amino acidergic ....serotonergic , amino acids: amino acidergic ....

AcetylcholineAcetylcholine: In neuromuscular junction (NMJ), : In neuromuscular junction (NMJ), preganglionic ANS, postganglionic parasym., basal preganglionic ANS, postganglionic parasym., basal forebrain & brain stem complexes. Synthesized forebrain & brain stem complexes. Synthesized from acetylcoenzyme-A & choline, catalyzed by from acetylcoenzyme-A & choline, catalyzed by cholineacetyltransferase enzyme (CAT), Ach is cholineacetyltransferase enzyme (CAT), Ach is degraded in cleft by acetylcholinesterase enzyme degraded in cleft by acetylcholinesterase enzyme (ACE), its receptors are (ACE), its receptors are nicotinicnicotinic(complex of 5 (complex of 5 αα or or ββ subunits) or subunits) or muscarinicmuscarinic receptors. Nicotinic: in receptors. Nicotinic: in NMJ, sym. ganglia, many parts of CNS, NMJ, sym. ganglia, many parts of CNS, Muscarinic in smooth muscles & glands.Muscarinic in smooth muscles & glands.

CAT Acetyl coenzyme A + choline Acetylcholine ACE Acetylcholine choline + acetate