1. Membrane potentials 膜电位 Xia Qiang, PhD Department of Physiology Zhejiang University School of Medicine Tel: 88206417, 88208252 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. 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）

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

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

8. 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:

9. 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:

10. Mammalian skeletal muscle cell -95 mV-90 mV Frog skeletal muscle cell -105 mV-90 mV Squid giant axon -96 mV-70 mV E k O bserved RP Difference between E K and directly measured resting potential

11. Goldman-Hodgkin-Katz equation

12. Electrogenic Hyperpolarizing Role of Na + -K + pump: 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!

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

15. 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

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

17. Electrotonic Potential （电紧张电位）

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

19. Graded potentials can be:EXCITATORYorINHIBITORY (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.

21. 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）

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

23. Ionic basis of action potential

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

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

27. 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. An action potential is an “all-or-none” sequence of changes in 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)

31. Mechanism of the initiation and termination of AP

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

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

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

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

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

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

40. Strength-duration Curve （强度 - 时间曲线）

41. 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）

42. 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）

44. Factors affecting excitability Resting potential Threshold Channel state

45. 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.

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

47. 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

48. 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; 585-587 Biochem 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.

49. 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!

50. 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

51. 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

52. 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 voltage B. the depolarization peak will remain the same C. the depolarization peak will reach a lower voltage

53. THANK YOU!