Membrane potentials

1. Membrane potentials XIA Qiang, MD & PhD Department of Physiology Room 518, Block C, Research Building School of Medicine, Zijingang Campus Email: xiaqiang@zju.edu.cn Tel: 88206417 (Undergraduate school), 88208252 (Medical school)

2. OUTLINE Resting potential Graded potential Action potential Refractory period

3. Electrocardiogram ECG

4. Electroencephalogram EEG

5. Electromyogram EMG

6. Extracellular Recording

7. Intracellular Recording

8. Opposite charges attract each other and will move toward each other if not separated by some barrier.

9. Only a very thin shell of charge difference is needed to establish a membrane potential.

11. Resting membrane potential 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

12. 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. Depolarization occurs when ion movement reduces the charge imbalance. Hyperpolarization is the development of even more negative charge inside the cell.

13. unequal ion distribution (chemical gradient) across the membrane • selective membrane permeability (cell membrane is more permeable to K+) • Na+-K+ pump

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

15. The Nernst Equation: K+ equilibrium potential (EK) (37oC) R=Gas constant T=Temperature Z=Valence F=Faraday’s constant

16. 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.

17. 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.

18. 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

19. Goldman-Hodgkin-Katz equation

20. 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!

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

23. Electrotonic Potential

24. Graded potential Graded potentials are changes in membrane potential that are confined to a relative small region of the plasma membrane

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

26. 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.

27. Graded potentials decay as they move over distance.

28. Graded potentials (Local response, local excitation, local potential) • Not “all-or-none” • Electrotonic propagation: spreading with decrement • Summation: spatial & temporal

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

30. Excitable cells: a cell in which the membrane response to depolarisations is nonlinear, causing amplification and propagation of the depolarisation (an action potential). Action potential 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

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

32. Ionic basis of action potential

33. (1) Depolarization: Activation of voltage-gated Na+ channel Blocker: Tetrodotoxin (TTX)

34. (2) Repolarization: Inactivation of Na+ channel Activation of K+ channel Blocker: Tetraethylammonium (TEA)

36. 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.

39. 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)

40. Click here to play the Voltage Gated Channels and Action Potential Flash Animation

41. Mechanism of the initiation and termination of AP

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

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

46. Nobel Prize in Physiology or Medicine 1963 • "for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane" • Eccles Hodgkin Huxley How to study ? • Voltage Clamp

47. Currents recorded under voltage clamp condition

48. Nobel Prize in Physiology or Medicine 1991 • "for their discoveries concerning the function of single ion channels in cells" • Erwin Neher Bert Sakmann • Patch Clamp

50. Conduction of action potential Continuous propagation in the unmyelinated axon