membrane potentials 膜电位 xia qiang, phd department of physiology room c518, block c, research...

Membrane potentials膜电位

Xia Qiang, PhD

Department of PhysiologyRoom C518, Block C, Research Building, ZJU School of MedicineTel: 88208252Email: xiaqiang@zju.edu.cn

Resting membrane potential（静息电位）

A potential difference across the membranes of inactive cells, with the inside of the cell negative relative to the outside of the cell

Ranging from –10 to –100 mV

Depolarization occurs when ion movement reduces the charge imbalance.

A cell is “polarized” because its interior is more negative than its exterior.

Overshoot refers to the development of a charge reversal.

Repolarization is movement back toward the resting potential.

Hyperpolarization is the development of even more negative charge inside the cell.

（极化）

（去极化） （超极化）

（复极化）

（超射）

chemical driving force

electrical driving force

++++++++++++++++

- - - - - - - - - - - - - - - - -electrochemic

al balance

The Nernst Equation:

K+ equilibrium potential (EK) (37oC)i

o

Ion

Ion

ZF

RTE

][

][log

R=Gas constantT=TemperatureZ=ValenceF=Faraday’s constant

)(][

][log60 mV

K

KEk

i

o

（钾离子平衡电位）

Begin: K+ in Compartment 2, Na+ in Compartment 1; BUT only K+ can move.

Ion movement: K+ crosses into Compartment 1; Na+ stays in Compartment 1.

buildup of positive charge in Compartment 1 produces an electrical potential that exactly offsets the K+ chemical concentration gradient.

At the potassium equilibrium potential:

Begin: K+ in Compartment 2, Na+ in Compartment 1; BUT only Na+ can move.

Ion movement: Na+ crosses into Compartment 2; but K+ stays in Compartment 2.

buildup of positive charge in Compartment 2 produces an electrical potential that exactly offsets the Na+ chemical concentration gradient.

At the sodium equilibrium potential:

Mammalian skeletal muscle cell -95 mV-90 mV

Frog skeletal muscle cell -105 mV -90 mV

Squid giant axon -96 mV -70 mV

Ek Observed RP

Difference between EK and directly

measured resting potential

Goldman-Hodgkin-Katz equation

•Electrogenic

•Hyperpolarizi

ng

Role of Na+-K+ pump:

Establishment of resting membrane potential:Na+/K+ pump establishes concentration gradientgenerating a small negative potential; pump uses up to 40% of the ATP produced by that cell!

Origin of the normal resting membrane potential

K+ diffusion potential

Na+ diffusion

Na+-K+ pump

Action potential（动作电位）

Some of the cells (excitable cells) are capable to rapidly reverse their resting membrane potential from negative resting values to slightly positive values. This transient and rapid change in membrane potential is called an action potential

Negative after-

potential

Positive after-

potential

Spike potential After-potential

A typical neuron action potential

Electrotonic Potential（电紧张电位）

The size of a graded potential(here, graded depolarizations) is proportionate to the intensity of the stimulus.

Graded potentials can be: EXCITATORY or INHIBITORY (action potential (action potential is more likely) is less likely)

The size of a graded potential is proportional to the size of the stimulus.

Graded potentials decay as they move over distance.

Graded potentials decay as they move over distance.

Local response（局部反应）

•Not “all-or-none” （全或

无）

•Electrotonic

propagation: spreading

with decrement （电紧张

性扩布）

•Summation: spatial &

temporal （时间与空间总和

）

Threshold Potential（阈电位） : level of depolarization needed to

trigger an action potential (most neurons have a threshold at -50 mV)

Ionic basis of action potential

(1) Depolarization（去极化） :

Activation of Na+ channel

Blocker:

Tetrodotoxin

(TTX)

（河豚毒素）

(2) Repolarization（复极化） :

Inactivation of Na+ channel

Activation of K+ channel

Blocker:

Tetraethylammoni

um

(TEA)（四乙胺）

The rapid opening of voltage-gated Na+ channels explains the rapid-depolarization phase at the beginning of the action potential.

The slower opening of voltage-gated K+ channels explains the repolarization and after hyperpolarization phases that complete the action potential.

An action potentialis an “all-or-none”sequence of changesin membrane potential.

Action potentials result from an all-or-none sequence of changes in ion permeability due to the operation of voltage-gated Na+ and K + channels.

The rapid opening of voltage-gated Na+ channels allows rapid entry of Na+, moving membrane potential closer to the sodium equilibrium potential (+60 mv)

The slower opening of voltage-gated K+ channels allows K+ exit, moving membrane potential closer to the potassium equilibrium potential (-90 mv)

Mechanism of the initiation and termination of AP

Re-establishing Na+ and K+ gradients after AP

Na+-K+ pump

“Recharging”

process

Properties of action potential (AP)

•Depolarization must exceed threshold

value to trigger AP

•AP is all-or-none

•AP propagates without decrement

Conduction of action potential（动作电位的传导）

Continuous propagation in the unmyelinated axon

Saltatory propagation in the myelinated axon

http://www.brainviews.com/abFiles/AniSalt.htm

Saltatorial Conduction: Action potentials jump from one node to thenext as they propagate along a myelinated axon.（跳跃性传导）

Excitation and Excitability（兴奋与兴奋性）

To initiate excitation (AP) Excitable cells Stimulation

Intensity

Duration

dV/dt

Strength-duration Curve（强度 -时间曲线）

Four action potentials, each the result of a stimulus strong enough to cause depolarization, are shown in the right half of the figure.

Threshold intensity（阈强度） & Threshold stimulus（阈刺激）

Refractory period following an AP:1. Absolute Refractory Period: inactivation of Na+

channel（绝对不应期）2. Relative Refractory Period: some Na+ channels

open（相对不应期）

Factors affecting excitability

Resting potential

Threshold

Channel state

The propagation of the action potential from the dendritic to the axon-terminal end is typically one-way because the absolute refractory period follows along in the “wake” of the moving action potential.

SUMMARY

Resting potential: K+ diffusion potential Na+ diffusion Na+ -K+ pump

Graded potential Not “all-or-none” Electrotonic propagation Spatial and temporal summation

Action potential Depolarization: Activation of voltage-

gated Na+ channel Repolarization: Inactivation of Na+

channel, and activation of K+ channel

Refractory period Absolute refractory period Relative refractory period

Sydney Ringer published 4 papers in the Journal of Physiology in 1882 and 1883, while working as a physician in London.

Sydney Ringer and his work on ionic composition of buffers

He found that 133mM NaCl, 1.34mM KCl, 2.76mM NaHCO3 1.25mM CaCl2 could sustain the frog heart beat.

J Physiol 2004, 555.3; 585-587Biochem J 1911, 5 (6-7).

1835-1910

He wrote “The striking contrast between potassium and sodium with respect to this modification (wrt refractoriness) is of great interest….because, from the chemical point of view, it would be quite unlooked for in two elements apparently so akin”

Ringer found that in excess potassium the period of diminished excitability is increased, and frequnecy of heart beats diminishes.

A rather somber application note: Death by lethal injection

Lethal injection is used for capital punishment in some states with the death penalty. Lethal injection consists of (1) Sodium thiopental (makes person unconscious), (2) Pancuronium/tubocurare (stops muscle movement), (3) Potassium chloride (causes cardiac arrest).

It seems a bit sick, but we can understand how this works from what we know about electrical signalling. Recall that

iNaiK

oNaoK

NaPKP

NaPKPmVVm

][][

][][log54.61

10

ii

oomVVm]15[1]100[40

]150[1]5[40log54.61

10

mVmVVm 654015

350log54.61

10

ii

oomVVm]15[1]100[40

]150[1]95[40log54.61

10

mVmVVm 4.04015

3950log54.61

10

This explains what Sydney Ringer observed in frog hearts in 1882!

If a negatively charged ion is more concentrated inside of a cell, is the equilibrium potential for that ion positive or negative? (make a drawing if it helps)

A. positiveB. negative

In a cell, if the equilibrium potential for Na+ is +50 mV and the equilibrium potential for K+ is -50 mV, what is the membrane potential if the membrane is equally permeable to Na+ and K+?

A. +50 mVB. +25 mVC. 0 mVD. -25 mVE. -50 mV

If the voltage-gated Na+ channel is modified so it inactivates more rapidly, how will the action potential change?

A. the depolarization peak will reach a higher voltageB. the depolarization peak will remain the sameC. the depolarization peak will reach a lower voltage

THANK YOU!