1. Membrane potentials膜电位 Xia Qiang, PhD Department of Physiology Room C518, Block C, Research Building, ZJU School of Medicine Tel: 88208252 Email: xiaqiang@zju.edu.cn

3. 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

4. （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）

5. electrochemical balance - - - - - - - - - - - - - - - - - ++++++++++++++++ chemical driving force electrical driving force

6. 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）

7. 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.

8. 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.

9. Difference between EK and directly measured resting 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

10. Goldman-Hodgkin-Katz equation

11. 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!

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

14. 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

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

16. Electrotonic Potential（电紧张电位）

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

18. 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.

19. Graded potentials decay as they move over distance.

20. 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）

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

22. Ionic basis of action potential

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

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

26. 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.

29. 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)

30. Mechanism of the initiation and termination of AP

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

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

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

36. Saltatory propagation in the myelinated axon http://www.brainviews.com/abFiles/AniSalt.htm

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

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

39. Strength-duration Curve（强度-时间曲线）

40. 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.

41. 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）

43. Factors affecting excitability • Resting potential • Threshold • Channel state

44. 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.

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

46. 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

47. 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. 1835-1910 J Physiol 2004, 555.3; 585-587 Biochem J 1911, 5 (6-7).

48. A rather somber application note: Death by lethal injection This explains what Sydney Ringer observed in frog hearts in 1882! 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

49. 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. positive B. negative

50. 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 mV B. +25 mV C. 0 mV D. -25 mV E. -50 mV