• chap. 2 The resting membrane

potential• chap. 3 Action potential

第二章 细胞的兴奋

from Berne & Levy Principles of

Physiology

(4th ed)

2005

• chap. 16 Electrical activity of

the heart• chap. 17 Natural excitation of the

heart

Observations of Membrane Potentials

4. ACTION PONTIELS

1. IONIC EQUILIBRIA

2. RESTING MEMBRANE POTENTIALS

3. SUBTHRESHOLD RESPONSES

5. 心肌细胞和起搏细胞的动作电位

Observations of Membrane Potentials

• Extracellular recording

• Intracellular recording

• Voltage clamp

macroscopical current

• Patch clamp

single channel current

1. IONIC EQUILIBRIA

Concentration force Electrical force

Electrochemical Equilibrium

• When the force caused by the concentration

difference and the force caused by the

electrical potential difference are equal and

opposite, no net movement of the ion occurs,

and the ion is said to be in electrochemical

equilibrium across the membrane.• When an ion is in electrochemical

equilibrium, the electrochemical potential

difference is called as equilibrium potential or

Nernst potential.

The Nernst Equation

B

ABAX X

X

zF

RTEEE

][

][ln

Where

EX equilibrium potential of X+

R ideal gas constant

T absolute temperature

z charge number of the ion

F Faraday’s number

natural logarithm of concentration ration

of X+on the two sides of the membrane

B

A

X

X

][

][ln

• At any membrane potential other than the

Ex , there will be an electrochemical driving

force for the movement of X+ across the

membrane, which tend to pull the membrane

potential toward its EX.• The greater the difference between the

membrane potential and the EX will result in

a greater driving force for net movement of

ions.• Movement can only happen if there are open

channels!

Distribution of Ions Across Plasma Membranes

of a human skeletal muscle cell

2. RESTING MEMBRANE POTENTIALS

The cytoplasm is usually electrically

negative relative to the extracellular

fluid. This electrical potential difference

across the plasma membrane in a

resting cell is called the resting

membrane potential.

The Chord Conductance Equation

ClCl

NaNa

KK

m Eg

gE

g

gE

g

gE

where

Em membrane potential

Es equilibrium potentials of the ion s

gs conductance of the membrane to the

ion s. the more permeable, the greater

the conductance.

ClNaK gggg

• The Na+,K+-ATPase contributes directly to generation of the resting membrane potential.

• All the ions that the membrane is

permeable to contribute to the

establishment of the potential of the

membrane at rest.• 细胞膜在静息状态下对 K+ 的通透性一般大于其它离子（主要是 IK1 ），因此大多数细胞的静息膜电位都是胞内为负。

3. SUBTHRESHOLD RESPONSES

• The size (amplitude) of the subthreshold

potential is directly proportional to the

strength of the triggering event.

• A subthreshold potential can be either

hyperpolarizing (make membrane potential

more negative) or depolarizing (make

membrane potential more positive)

graded potential

• This passive spread of electrical

signals with no changes in membrane

property is known as electrotonic

conduction.

• Subthreshold potentials decrease in

strength as they spread from their point

of origin, i.e. conducted with decrement.

local response

spatial summation & temporal summation

4. ACTION PONTIELS

An action

potential is a

rapid change in

the membrane

potential followed

by a return to the

resting

membrane

potential.

action potential of a squid giant axon

• At peak of action potential membrane

potential reverses from negative to positive

(overshoot).

• During the hyperpolarizing afterpotential,

the membrane potential actually becomes

less negative than it is at rest.

• Rising phase (depolarization phase)

• Repolarization phase

• An action potential is triggered when the

depolarization is sufficient for the

membrane potential to reach a threshold.

Ionic Mechanisms of Action Potential

Km

KK EE

Ig

Nam

NaNa EE

Ig

changes of ion conductance during action potential

• Action potentials arise as a result of brief

alterations in the electrical properties of the

membrane.

• During the early part of the action

potential, the rapid increase in gNa causes

the membrane potential to move toward

ENa. • The rapid return of the action potential

toward the resting potential is caused by

the rapid decrease in gNa and the continued

increase in gK.

• Action potentials differ in size and shape

in different cells, but the fundamental

mechanisms underlying the initiation of

these potentials does not vary.

• During the hyperpolarizing

afterpotential, when the membrane

potential is actually more negative than

the resting potential, gNa returns to

baseline levels, but gK remains elevated

above resting levels.

model of the voltage-dependent Na+ channel

closed open inactivated

• 去极相： INa 激活，钠内流

枪乌贼巨轴突动作电位各个时期的主要电流

•超级化后电位： 膜电位复极到静息电位时， IK 仍然开放，钾继续外流使得膜电位超级化； 随着 IK 的缓慢关闭，膜电位逐渐回到静息电位。

• 复极相： INa 失活； IK 激活，钾外流

• Either a stimulus fails to elicit an action

potential or it produces a full-sized action

potential.

Properties of Action Potential

All-or-None Response

• The size and shape of an action potential

remain the same as the potential travels

along the cell.• The intensity of a stimulus is encoded by the

frequency of action potentials.

Refractory Period

relative refractory

period

absolute refractory

period

Conduction of Action Potential

Local circuit current Self-reinforcing

• myelination

Conduction velocity • diameter

saltatory conduction

5. 细胞动作电位的多态性

心脏中两种细胞的动作电位

心肌细胞

起搏细胞

心肌细胞动作电位的波形

4 期：静息期

•0 期：快速去极化期 -90mV to +30mV,1~2ms

•1 期：快速复极化初期 +30mV to 0mV, 10ms

•2 期：平台期 0mV, 100~150ms

•3 期：快速复极化末期 0mV to -90mV, 100~150ms

心肌细胞动作电位的离子机制

心肌细胞动作电位不同时期的主要离子通道

IK1 ：内向整流钾通道

•INa ：快钠通道 激活和失活的速率很快•Ica,L ： L 型钙通道 激活电位约 -30mV ，激活速度较慢（ 约 20ms ）， 失活速度很慢（约 500ms ）•Ito ：瞬时外向钾通道 激活（约 2ms ）和失活（ 20ms ）都相对较快•IK ：延迟整流钾通道 缓慢激活和失活（ 200~1000ms ）， 激活后电流随膜电位呈现整流性质

心肌细胞动作电位各个时期的主要电流

•1 期：快速复极化初期 INa 失活； Ito 激活，钾外流

•0 期：快速去极化期 INa 激活，钠内流

•3 期：快速复极化末期 Ica,L 逐渐失活， IK 进一步激活，钾外流•4 期：静息期 IK 关闭； IK1 电流增强

•2 期：平台期 Ito 失活； IK1 通透性降低； IK 和 Ica,L 激活，钾外流和钙内流相当

IK1 的内向整流特性

心肌细胞动作电位的不应期

起搏细胞动作电位的波形

• 0 期：去极化 -40mV to +15mV, 7ms• 3 期：复极化 +15mV to -70mV, 约 100ms• 4 期：自动去极化 -70mV to -40mV

• Ica,T ： T 型钙通道 激活电位约 -50mV ， 激活速度很快（约 2ms ）， 失活速度很快（约 20~30ms ）

起搏细胞动作电位相关离子通道

• If ：环式核苷酸门控阳离子通道 膜电位从 -50mV 向超级化变化时缓慢激活 激活后以钠内流为主

起搏细胞动作电位的离子机制

• 0 期： Ica,L 激活开放，钙内流• 3 期： IK 激活开放，钾外流• 4 期： IK 关闭，钾外流进行性衰减 If 电流（主要是钠内流）进行性增强 后期 Ica,L 激活开放，少量钙内流

起搏细胞动作电位各个时期的主要电流