1. Membrane potentials 膜电位
Xia Qiang, PhD
Department of Physiology
Zhejiang University School of Medicine
Tel:

2. LEARNING OBJECTIVES
Describe the maintenance of resting potential in a cell
Explain how a cell is induced exciting
Contrast graded potentials and action potentials
Describe how a cell has refractory phase

4. 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

5. （超射） （复极化） （极化） （超极化） （去极化） Overshoot refers to the development of
a charge reversal.
（超射）
A cell is
“polarized”
because
its interior
is more
negative
than its
exterior.
Repolarization is
movement back
toward the
resting potential.
（复极化）
（极化）
Depolarization
occurs
when ion
movement
reduces the
charge
imbalance.
Hyperpolarization is
the development of
even more negative
charge inside the cell.
（超极化）
（去极化）

6. electrochemical balance
chemical driving force
electrochemical balance
electrical driving force

7. A membrane potential results from separation of positive and negative charges across the cell membrane. The excess of positive charges (red circles) outside the cell and negative charges (blue circles) inside the cell at rest represents a small fraction of the total number of ions present

8. R=Gas constant T=Temperature Z=Valence F=Faraday’s constant （钾离子平衡电位）
The Nernst Equation:
K+ equilibrium potential (EK) (37oC)
R=Gas constant
T=Temperature
Z=Valence
F=Faraday’s constant
（钾离子平衡电位）

9. 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:

10. 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:

11. Difference between EK and directly measured resting potential
Ek Observed RP
Mammalian skeletal muscle cell -95 mV -90 mV Frog skeletal muscle cell -105 mV -90 mV Squid giant axon -96 mV -70 mV

12. Goldman-Hodgkin-Katz equation
The systemic inflammatory response syndrome (SIRS) is a clinical response arising from a nonspecific insult manifested by two or more of the following:
Fever or hypothermia
Tachycardia
Tachypnea
Leukocytosis, leukopenia, or a left-shift (increase in immature neutrophilic leukocytes in the blood)
Recent evidence indicates that hemostatic changes play a significant role in many SIRS-linked disorders.
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med. 2000; 28:S81-2.
Goldman-Hodgkin-Katz equation

13. Role of Na+-K+ pump: Electrogenic Hyperpolarizing
Establishment of resting membrane potential:
Na+/K+ pump establishes concentration gradient
generating a small negative potential; pump
uses up to 40% of the ATP produced by that cell!
The systemic inflammatory response syndrome (SIRS) is a clinical response arising from a nonspecific insult manifested by two or more of the following:
Fever or hypothermia
Tachycardia
Tachypnea
Leukocytosis, leukopenia, or a left-shift (increase in immature neutrophilic leukocytes in the blood)
Recent evidence indicates that hemostatic changes play a significant role in many SIRS-linked disorders.
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med. 2000; 28:S81-2.

14. Origin of the normal resting membrane potential
K+ diffusion potential
Na+ diffusion
Na+-K+ pump

16. 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

17. Negative after-potential
A typical neuron action potential
Positive
after-potential
Negative after-potential
Spike potential After-potential

18. Electrotonic Potential（电紧张电位）

19. Electrotonic potentials and local response
Electrotonic potentials and local response. The changes in the membrane potential of a neuron following application of stimuli of 0.2, 0.4, 0.6, 0.8, and 1.0 times threshold intensity are shown superimposed on the same time scale. The responses below the horizontal line are those recorded near the anode, and the responses above the line are those recorded near the cathode. The stimulus of threshold intensity was repeated twice. Once it caused a propagated action potential (top line), and once it did not.

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

21. Graded potentials can be:. EXCITATORY. or. INHIBITORY
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.

22. Graded potentials decay as they move over distance.

23. 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）

24. Threshold Potential（阈电位）: level of depolarization needed to trigger an action potential (most neurons have a threshold at -50 mV)

25. Ionic basis of action potential

26. (1) Depolarization（去极化）:
Activation of Na+ channel
Blocker:
Tetrodotoxin (TTX)
（河豚毒素）

27. (2) Repolarization（复极化）:
Inactivation of Na+ channel
Activation of K+ channel
Blocker:
Tetraethylammonium
(TEA)（四乙胺）

29. 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.

30. Changes in membrane potential and relative membrane permeability to Na+ and K+ during an action potential. Steps 1 through 7 are detailed in the text. These changes in threshold for activation (excitability) are correlated with the phases of the action potential.

31. Feedback control in voltage-gated ion channels in the membrane
Feedback control in voltage-gated ion channels in the membrane. A) Na+ channels exert positive feedback. B) K+ channels exert negative feedback. PNa, PK is permeability to Na+ and K+, respectively.

32. voltage-gated Na+ channels allows rapid entry of Na+,
An action potential
is an “all-or-none”
sequence of changes
in membrane potential.
The rapid opening of
voltage-gated Na+ channels
allows rapid entry of Na+,
moving membrane potential
closer to the sodium
equilibrium potential (+60 mv)
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 slower opening of
voltage-gated K+ channels
allows K+ exit,
moving membrane potential
closer to the potassium
equilibrium potential (-90 mv)

33. Mechanism of the initiation and termination of AP

34. Re-establishing Na+ and K+ gradients after AP
Na+-K+ pump
“Recharging” process

35. Properties of action potential (AP)
Depolarization must exceed threshold value to trigger AP
AP is all-or-none
AP propagates without decrement

38. Conduction of action potential（动作电位的传导）
Continuous propagation in the unmyelinated axon

39. Local current flow (movement of positive charges) around an impulse in an axon. Top: Unmyelinated axon. Bottom: Myelinated axon. Positive charges from the membrane ahead of and behind the action potential flow into the area of negativity represented by the action potential (“current sink”). In myelinated axons, depolarization appears to “jump” from one node of Ranvier to the next (saltatory conduction).

40. Saltatory propagation in the myelinated axon

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

42. Excitation and Excitability （兴奋与兴奋性）
To initiate excitation (AP)
Excitable cells
Stimulation
Intensity
Duration
dV/dt

43. Strength-duration Curve（强度-时间曲线）

44. Threshold intensity（阈强度） & Threshold stimulus（阈刺激）
Four action potentials, each the result of a stimulus strong enough to cause depolarization, are shown in the right half of the figure.

45. 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）

47. Factors affecting excitability
Resting potential
Threshold
Channel state

48. 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.

49. SUMMARY Resting potential: Graded potential K+ diffusion potential
Na+ diffusion
Na+ -K+ pump
Graded potential
Not “all-or-none”
Electrotonic propagation
Spatial and temporal summation

50. Action potential Refractory period
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

51. Sydney Ringer and his work on ionic composition of buffers
Sydney Ringer published 4 papers in the Journal of Physiology in 1882 and 1883, while working as a physician in London.
He found that
133mM NaCl,
1.34mM KCl,
2.76mM NaHCO3
1.25mM CaCl2
could sustain the frog heart beat.
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.
J Physiol 2004, 555.3;
Biochem J 1911, 5 (6-7).

52. 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
This explains what Sydney Ringer observed in frog hearts in 1882!

53. THANK YOU!