Understanding Membrane Potentials in Physiology

1. Membrane potentials膜电位 Xia Qiang, PhD Department of Physiology Zhejiang University School of Medicine Tel: 88206417 Email: xiaqiang@zju.edu.cn

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） Overshoot refers to the development of a charge reversal. 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 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. 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. At the potassium equilibrium potential: buildup of positive charge in Compartment 1 produces an electrical potential that exactly offsets the K+ chemical concentration gradient.

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

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

12. 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!

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. 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. 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 (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. A) Na+ channels exert positive feedback. B) K+ channels exert negative feedback. PNa, PK is permeability to Na+ and K+, respectively.

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

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

50. 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