Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane...

20
1 Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. Passive Membrane 2. Resting Potential 3. Dendrites/Axons as Cables 4. Properties of Action Potential 5. Hodgkin/Huxley Model Passive Membrane Model 2 / 1 cm F C µ

Transcript of Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane...

Page 1: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

1

Membrane Models and the Hodgkin/HuxleyModel of the Action Potential

1. Passive Membrane2. Resting Potential3. Dendrites/Axons as Cables4. Properties of Action Potential5. Hodgkin/Huxley Model

Passive Membrane Model

2/1 cmFC µ≈

Page 2: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

2

R

VVI

dt

dVC rm

injm )( −+=

rV

RIV injr +

injI

t

Page 3: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

3

int

ext

int

extBKK K

K

zF

RT

K

K

q

TkVE

][

][ln

][

][ln ===

Nernst Potential

int

extKK K

K

z

mVVE

][

][log

58==

[K]int>[K]ext

resting potentialis negative

Goldman Hodgkin Katz Equation

extClintNaintK

intClextNaextK

ClPNaPKP

ClPNaPKPV

][][][

][][][log58

++++=

ClNaK PPP :: relative permeabilities

ClNaK PPP ,>>

ClKNa PPP ,>>KNaCl PPP ,>>

KV

ClV

NaV

Page 4: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

4

Spheres and Cables

Frog muscle fiber (Fatt and Katz, 1951)

Page 5: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

5

lobster axon,Hodgkin andRushton, 1946

mm3.1≈λ

Membrane potential decay from point ofconstant current injection

),(),(1

2

2txi

x

txV

r mm

a=

∂∂

),(),(

),( txIt

Vc

r

VtxVtxi inj

mm

m

restmm −

∂∂+−=

),()),((),(),(

2

22 txIrVtxV

t

txV

x

txVinjmrestm

mm

m −−+∂

∂=∂

∂ τλ

mmm cr=τ

a

m

r

r=λ

units:

rm: ohm-cm

ra: ohm/cm

im: A/cm

cm: F/cm

Page 6: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

6

)/exp()( 0 λxVxV −=

experiment

theory

temporal distributionat different locations

Page 7: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

7

refractory period

Adrian and Lucas, 1912

Page 8: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

8

Accomodation

Valibo, 1964Xenopus laevis nerve fiber

Squid Giant Axon

Page 9: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

9

mVVK 77−=

mVVNa 50+=

mVVL 4.54−=

Space Clamp/Voltage Clamp

Page 10: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

10

Cole, 1968

Bernstein TheoryPermeability to K at rest

Membrane breaks down transiently

Na+ permeabilitychange associated

with peak

Page 11: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

11

cm

mcmo

VK

KV

VVKVV

1

)(

+=

−==

Voltage Clamp

voltagecommandVc =

Page 12: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

12

commandvoltages

separating the currentsby altering Nernst

potential

Page 13: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

13

)( KKK VVgI −=

gating driving force

)( NaNaNa VVgI −=

)( LLL VVgI −=

Ohmic for each stateV: mV

g : m mho/cm2

Ι : µA/cm2

units:

Page 14: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

14

))(()1)(( nVnVdt

dnnn βα −−=

)/exp()()( 0 ntnnntn τ−−−= ∞∞

nnn βα

τ+

= 1

nn

nnβα

α+

=∞

),(),( 4 tVngtVg KK =

α,β: msec-1

g : m mho/cm2

n : [0,1]

units:τ: msec

maximum conductance (constant)

)4exp()exp()(1 tgttnndt

dnn nKnn βββ −≈⇒−≈⇒−≈⇒≈

4)()(0 tgttndt

dnn nKnn ααα ≈⇒≈⇒≈⇒≈

)(4KKK VVngg −=

))(()1)(( nVnVdt

dnnn βα −−=

Page 15: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

15

))(()1)(( mVmVdt

dmmm βα −−=

),(),(),( 3 tVhtVmgtVg NaNa =

))(()1)(( hVhVdt

dhhh βα −−=

α,β: msec-1

g : m mho/cm2

m,h : [0,1]units:

m fast

m,n activate with depolarization

h inactivates with depolarization

Page 16: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

16

nn

n

τα ∞=

nn

n

τβ ∞−= 1

α,β: msec-1units: V: mV

]10/)55(exp[1

)55(01.0)(

+−−+=

V

VVnα

]10/)40(exp[1

)40(1.0)(

+−−+=

V

VVmα

]20/)65(exp[07.0)( +−= VVhα ]10/)35(exp[1

1)(

+−+=

VVhβ

]80/)65(exp[125.0)( +−= VVnβ

]18/)65(exp[4)( +−= VVmβ

nn

n

τα ∞=

nn

n

τβ ∞−= 1

α,β: msec-1units: V: mV

Page 17: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

17

]10/)55(exp[1

)55(01.0)(

+−−+=

V

VVnα

]10/)40(exp[1

)40(1.0)(

+−−+=

V

VVmα

]20/)65(exp[07.0)( +−= VVhα ]10/)35(exp[1

1)(

+−+=

VVhβ

]80/)65(exp[125.0)( +−= VVnβ

]18/)65(exp[4)( +−= VVmβ

)()()( 43LLKKNaNa VVgVVngVVhmgI

dt

dVC −−−−−−=

))(()1)(( mVmVdt

dmmm βα −−=

))(()1)(( hVhVdt

dhhh βα −−=

))(()1)(( nVnVdt

dnnn βα −−=

Space Clamped Hodgkin/Huxley Model

2/120 cmmmhogNa =2/36 cmmmhogK =2/3.0 cmmmhogL =

mVVNa 50=

mVVK 77−=

mVVL 4.54−=2/1 cmFC µ=

2/: cmAI µmVV :

numerical integration of H/H equations

Page 18: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

18

)()()( 43LLKKKNa VVgVVngVVhmg

t

VCI −+−+−+

∂∂=

2

2

2 x

V

R

aI

∂∂= cm)(kyresistivitlarintracelluspecific

(cm)radius

Ω==

R

a

)()()(2

432

2

2 LLKKKNa VVgVVngVVhmgdt

dVC

dt

Vd

R

a −+−+−+=θ

)(),(assume txVtxV θ−=

(cm/msec)velocitygpropagatin=θ

integrateynumericall,guessθ

2

2

22

2 1

t

V

x

V

∂∂=

∂∂

θ

Page 19: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

19

Cooley & Dodge

PDEODE

Page 20: Membrane Models and the Hodgkin/Huxley Model of the …moehlis/APC591/Lecture2.pdf · Membrane Models and the Hodgkin/Huxley Model of the Action Potential 1. ... INa =gNa(V −VNa)

20