Physiology of The NervePhysiology of The Nerve

Week 4Week 4

Dr. Walid DaoudDr. Walid Daoud

A. ProfessorA. Professor

NeuronNeuron

Neuron or nerve cell is specialized for Neuron or nerve cell is specialized for transfer and integration of informationtransfer and integration of information..

Spinal Motor NeuronSpinal Motor Neuron::

- -Cell body (soma)Cell body (soma)..

- -DendritesDendrites for perception of signals from for perception of signals from other neurons other neurons . .

- -Axon (nerve fiber)Axon (nerve fiber) carries impulse away carries impulse away from the cell body from the cell body . .

Types of Nerve FibersTypes of Nerve Fibers11--Myelinated Nerve FibersMyelinated Nerve Fibers::

. .Surrounded by myelin sheath made by Surrounded by myelin sheath made by Schwann cells Schwann cells..

. .Myelin sheath is insulator to ion flowMyelin sheath is insulator to ion flow..

. .Nodes of Ranvier are non-insulated areasNodes of Ranvier are non-insulated areas..

e.g Preganglionic autonomic nerve fiberse.g Preganglionic autonomic nerve fibers..

22--Unmyelinated Nerve FibersUnmyelinated Nerve Fibers::

. .Axons not surrounded by myelin sheathAxons not surrounded by myelin sheath..

e.g Postganglionic autonomic nerve fiberse.g Postganglionic autonomic nerve fibers..

Electrical properties of NeuronElectrical properties of Neuron

ExcitabilityExcitability::

It is the ability of generating electrochemical It is the ability of generating electrochemical impulse (action potentials) at the cell impulse (action potentials) at the cell membrane in response to any stimulusmembrane in response to any stimulus..

ConductivityConductivity::

It is the ability to propagate action potential It is the ability to propagate action potential from the point of generation to the rest of from the point of generation to the rest of the membranethe membrane..

Nerve ExcitabilityNerve ExcitabilitySelective permeability of cell membrane Selective permeability of cell membrane causes difference in ionic composition of causes difference in ionic composition of intracellular and extracellular fluids intracellular and extracellular fluids creating a membrane potential which is creating a membrane potential which is the basis of excitabilitythe basis of excitability..Mainly intracellular ionsMainly intracellular ions::

Potassium, proteins, magnesium, phosphatePotassium, proteins, magnesium, phosphateMainly extracellular ionsMainly extracellular ions::

Sodium, chloride, bicarbonateSodium, chloride, bicarbonate

Factors affecting effectiveness of a stimulusFactors affecting effectiveness of a stimulus

11 - -StrengthStrength::Threshold stimulus or Rheobase Threshold stimulus or Rheobase is the is the minimal stimulus needed to excite the minimal stimulus needed to excite the nerve and produce action potentialnerve and produce action potential..

22 - -DurationDuration::Utilization timeUtilization time is the minimal time needed is the minimal time needed by Rheobase to give a responseby Rheobase to give a response..

ChronaxieChronaxie is the time needed by a stimulus is the time needed by a stimulus of 2 Rheobase to excite the nerveof 2 Rheobase to excite the nerve..It is a measure of nerve excitabilityIt is a measure of nerve excitability..

Resting Membrane Potential (RMP)Resting Membrane Potential (RMP)

It is the difference in electric potential (voltage) It is the difference in electric potential (voltage) between the inside and outside the between the inside and outside the membrane under resting conditions with the membrane under resting conditions with the inside negative and the outside positiveinside negative and the outside positive..

RMP is recorded by 2 microelectrodes RMP is recorded by 2 microelectrodes connected to a voltmeterconnected to a voltmeter..

RMP in large nerve fibers -90 mvRMP in large nerve fibers -90 mv

RMP in medium nerve fibers -70 mvRMP in medium nerve fibers -70 mv

RMP in red cells -20 mvRMP in red cells -20 mv

Causes of RMPCauses of RMP

11--Selective permeability of cell membraneSelective permeability of cell membrane Being 100 times more permeable to KBeing 100 times more permeable to K++ than to than to NaNa++ and impermeable to protein anions and impermeable to protein anions..

22--NaNa++ – K – K++ pump pump

Against concentration and electric gradient and Against concentration and electric gradient and this needs energy derived from cell membrane this needs energy derived from cell membrane ATPase activityATPase activity..

33 NaNa++ ions pumped out while 2 K ions pumped out while 2 K++ ions pumped in ions pumped in leading to positive charge outsideleading to positive charge outside..

Calculation of RMPCalculation of RMPNernst Equation:Nernst Equation: equilibrium potential (E) equilibrium potential (E)

is membrane potential at which movement of is membrane potential at which movement of a certain ion (Naa certain ion (Na++ or K or K++) stops. This occurs ) stops. This occurs when the 2 opposing forces (electrical and when the 2 opposing forces (electrical and chemical gradients) become equalchemical gradients) become equal..

E = +/- 61 log conc.inside / conc.outsideE = +/- 61 log conc.inside / conc.outside

E for KE for K++ = - 94 mv = - 94 mv

E for NaE for Na++ = +61 mv = +61 mv

This means that if KThis means that if K+ + is the only factor causing is the only factor causing RMP, RMP would equal -94 mvRMP, RMP would equal -94 mv..

Calculation of RMPCalculation of RMP

Goldman Equation: Goldman Equation: more accurate as it more accurate as it considerconsider::

- -NaNa++, K, K++ and Cl and Cl- - conc.inside and outside the conc.inside and outside the nerve fiber nerve fiber..

-- KK++ permeability is 100 times as that of Na permeability is 100 times as that of Na++..

RMP by diffusion of ions = -86 mv (near to RMP by diffusion of ions = -86 mv (near to KK+ + equilibrium potential)equilibrium potential)..

Action PotentialAction Potential - -It is the rapid change in the resting It is the rapid change in the resting

membrane potential following stimulation membrane potential following stimulation of a nerve by threshold stimulusof a nerve by threshold stimulus..

- -It is a process of depolarization (NaIt is a process of depolarization (Na++ influx) influx) followed by repolarization (K followed by repolarization (K++ efflux) efflux)..

- -Can be recorded by 2 microelectrodes Can be recorded by 2 microelectrodes connected to cathode ray oscilloscope connected to cathode ray oscilloscope . .

Steps and Phases of Action PotentialSteps and Phases of Action Potential

11 - -Stimulus artifactStimulus artifact..

22 - -Latent periodLatent period..

33 - -Ascending limb (Depolarization)Ascending limb (Depolarization)..

44 - -Descending limb (Repolarization)Descending limb (Repolarization)

Ionic Basis of Action PotentialIonic Basis of Action Potential

Depolarization is caused by Na inflow (influx)Depolarization is caused by Na inflow (influx)

Repolarization is caused by K outflow (efflux)Repolarization is caused by K outflow (efflux)

through 2 types of voltage-gated ion channelsthrough 2 types of voltage-gated ion channels::

11--Voltage-gated Na channel: 2 gatesVoltage-gated Na channel: 2 gates..

22--Voltage-gated K channel: one gateVoltage-gated K channel: one gate..

Once nerve is stimulatedOnce nerve is stimulated::

- - Outer Na gates open & inner Na gates closeOuter Na gates open & inner Na gates close

- - K gates openK gates open..

Successive movements of gates is Successive movements of gates is essential for production of action potentialessential for production of action potential

11--During DepolarizationDuring Depolarization:: - -Slow stageSlow stage from -90 mv to -65 mv which from -90 mv to -65 mv which

is the firing level is the firing level.. - -Rapid stageRapid stage from -65 mv to +35 mv from -65 mv to +35 mv..

22--During RepolarizationDuring Repolarization:: - - Inactivation of Na channelsInactivation of Na channels..

- - Activation of K channelsActivation of K channels..33--HyperpolarizationHyperpolarization::

Slow closure of K channelsSlow closure of K channels..

Action Potential in Nerve TrunkAction Potential in Nerve Trunk

Nerve trunk or peripheral nerves are made of Nerve trunk or peripheral nerves are made of many nerve fibersmany nerve fibers..

Action potential has many peaks (compound) Action potential has many peaks (compound) because each nerve fiber in the nerve because each nerve fiber in the nerve responds with responds with All or None RuleAll or None Rule..

Nerve fibers vary inNerve fibers vary in::

- -Threshold of stimulationThreshold of stimulation..

- -Distance from stimulating electrodeDistance from stimulating electrode,.,.

- -Speed of conductionSpeed of conduction..

Local response (local excitatory state)Local response (local excitatory state)

It is a slight depolarization caused by It is a slight depolarization caused by subthreshold stimulus which opens few Na subthreshold stimulus which opens few Na channels not enough to produce action channels not enough to produce action potential and repolarization follows rapidlypotential and repolarization follows rapidly..

- -Does not obey All or None RuleDoes not obey All or None Rule..

- -Can be gradedCan be graded..

- -Can be summatedCan be summated..

- -Not propagatedNot propagated . .

Excitability Changes During Action PotentialExcitability Changes During Action Potential

11 - -Absolute Refractory Period (ARP)Absolute Refractory Period (ARP)::

During which a second action potentialDuring which a second action potential

can not be elicited whatever is the strength can not be elicited whatever is the strength of the stimulus (excitability is zero) of the stimulus (excitability is zero)..

22 - -Relative Refractory Period (RRP)Relative Refractory Period (RRP)::

During which the nerve can not beDuring which the nerve can not be

stimulated unless the stimulus is strongerstimulated unless the stimulus is stronger

than usual (excitability is below normal)than usual (excitability is below normal)..

Factors Affecting Excitability of NerveFactors Affecting Excitability of Nerve

11--Increase excitabilityIncrease excitability::

--Increase Na permeability (Depolarize)Increase Na permeability (Depolarize)::

Low extracellular Ca, VeratrineLow extracellular Ca, Veratrine

- -Increase extracellular K concentrationIncrease extracellular K concentration..

22--Decrease excitability (membrane stabilizers)Decrease excitability (membrane stabilizers)

- -Decreased Na permeabilityDecreased Na permeability::

High extracellular Ca, local anesthesia:CocainHigh extracellular Ca, local anesthesia:Cocain

- -Decrease extracellular K concentrationDecrease extracellular K concentration . .

Nerve ConductivityNerve ConductivityAction potential once generated, it travels Action potential once generated, it travels along the length of the nerve fiber in both along the length of the nerve fiber in both directionsdirections..

Normally impulse travels in one direction i.e.Normally impulse travels in one direction i.e. Orthodromic conduction: Orthodromic conduction: from cell body from cell body along its axon to its terminationalong its axon to its termination..

Antiorthodromic conduction:Antiorthodromic conduction: is opposite is opposite..

Velocity of conduction is increased byVelocity of conduction is increased by increased diameter of nerve fiber & myelinincreased diameter of nerve fiber & myelin

Conduction in myelinated Nerve Fibers Conduction in myelinated Nerve Fibers (Salutatory Conduction)(Salutatory Conduction)

The action potentials are only generated at The action potentials are only generated at the nodes of Ranvier i.e action potential in the nodes of Ranvier i.e action potential in one node acts as stimulus for generation one node acts as stimulus for generation of new action potentials at adjacent nodesof new action potentials at adjacent nodes..

The positive charges jump from the resting The positive charges jump from the resting node to the adjacent active onenode to the adjacent active one..

Importance of Salutatory ConductionImportance of Salutatory Conduction::

--It increases velocity of conduction 50 foldsIt increases velocity of conduction 50 folds..

--It conserve energy for the axonIt conserve energy for the axon . .

Neuromuscular TransmissionNeuromuscular Transmission

Neuromuscular JunctionNeuromuscular Junction::

It is the area between nerve endings of alpha It is the area between nerve endings of alpha motor neurons and skeletal muscle fibersmotor neurons and skeletal muscle fibers..

Axon terminals of motor neuron (end feet or Axon terminals of motor neuron (end feet or Knobs) contain acetyl choline vesiclesKnobs) contain acetyl choline vesicles..

Motor end plateMotor end plate membrane contain acetyl membrane contain acetyl choline receptors and extracellular space choline receptors and extracellular space contains choline esterase enzymecontains choline esterase enzyme..

Steps of Neuromuscular TransmissionSteps of Neuromuscular Transmission

11 - -Arrival of action potentialArrival of action potential..

Nerve impulse increases permeability of Nerve impulse increases permeability of the membrane to Ca triggering rupture of the membrane to Ca triggering rupture of acetyl choline vesicles acetyl choline vesicles..

22 - -Postsynaptic responsePostsynaptic response..

33 - -End plate potentialEnd plate potential..

44 - -Acetyl choline degradationAcetyl choline degradation..

Properties of Neuromuscular JunctionProperties of Neuromuscular Junction

11 - -UnidirectionalUnidirectional..

22 - -DelayDelay..

33 - -FatigueFatigue..

44 - -Effects of ionsEffects of ions..

55 - -Effects of drugsEffects of drugs::

- -Drugs stimulate NMTDrugs stimulate NMT..

- - Drugs block NMTDrugs block NMT..