Resting potential

Action potential Excite State : 10mV Resting state : -90mV (Polarization) depolarization repolarization

Action potential

Action potential

Voltage clamp

Voltage clamp

Time Course of Action Potential t =0: 20mV pulse t =0.4ms: depolarization increase of Na+ current (passive, negative) t =0.6ms: voltage rise sharply t =0.8ms: increase of K+ current (passive, positive) t =1ms: dip in Na+ current (peak of action potential) t =1ms ~3.2ms: voltage decrease (small excessive K+ current )

Response to step depolarization Iion= INa+ IK A:Initial response from Na+ B:Replacement of extracellular fluid with choline Effect only on INa INaA /INaB = K(independent of time)

Conductance for K

Curve fitting 1 Estimation of n(v), n(v)  (v), (v) for each applied voltage v

Curve fitting 2 Estimation of n(v), n(v) as a function of voltage v n(v)=f(v) n(v)=fn(v) (v)= f(v) (v)= f(v)

Conductance for Na

Estimated parameters

Simulation

Change of Conductance  Voltage clamp  Na+ Channel  K+ Channel : 2ms pulse : channel selection - by single ion - by selective channel block  Na+ Channel : rapid channel open : slow channel closure  K+ Channel : slow activation : remain open for positive potential

 Onset of Action Potential  End of Action Potential Ratio of Conductance  Resting state - gK  100 • gNa - much greater leakage current  Onset of Action Potential - 5000 fold increase of gNa - positive feedback  End of Action Potential - negative potential - closure of K+ channel  Ratio of conductance - gNa /gK (middle curve)

 Equivalent membrane conductance Equivalent Circuit  Axon : axoplasm(conductor) : surrounded by insulating membrane(cable in sea water) : all of actions are in membrane(variable,nonlinear, imperfect insulator)  Equivalent membrane conductance : gNa --- Na+ ion : gK --- K+ ion : gCl --- Cl- ion (except Na+ & K+) 그림 3-7

Equations for model  I = IC + INa + IK + ICl = C(dV/dt)+ gNa(V-115)+ gK(V+12)+ gCl(V-10.6)  3 activity coefficients: m, n, h - gNa = 120m3h, - gK = 36n4 - gCl = 0.3 dm 0.1(25-V) dt e 0.1(25-V) - 1 = (1-m) - 4m e-V/18 dh 0.1(25-V) dt e 0.1(30-V) + 1 = 0.07e-V/20(1-h) - dn 0.01(10-V) dt e 0.1(10-V) - 1 = (1-n) - 0.125n e-V/80

Calculated Results  Peak Ion Currents  Peak net Currents - peak of lNa : -803 uA/cm2(at t=1.8ms) - peak of lK : 837 uA/cm2(at t=1.8ms) - peak lCl : 29 uA/cm2 (at t=0.9ms)  Peak net Currents - paek of lnet : -315 uA/cm2(at t=0.71ms) ( lNa=-417, lK=83, lCl=19 uA/cm2 ) 그림3-6

Voltage gated ion channel

Voltage gated ion channel

Voltage gated sodium channel

Bert Sakmann The Nobel Prize in Physiology or Medicine 1991

Propagation of action potential

Propagation of action potential

Axoplasm Rapid voltage attenuation 0.3um unmyelinated axon (smallest) V = Vine-x/0 : 0 = length constant fall to 37% of amplitude 0.3um unmyelinated axon (smallest) 0 = 0.15mm 1.3um unmyelinated neuron (largest) 0 = 0.33mm Length constant k•(axon diameter)1/2 may be viable for small organism length constant of 1mm  10 times increase of diameter (13um; unfeasible) 1.3um of copper wire 0 = 2800mm (8500 times more conductive)

Sensory vs Motor Neuron

Synapse

Synapse

Postsynaptic potential

Take home message Characteristics of action potential Propagation mechanism