1. Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical distribution of ions across the cell membrane AND the differential permeability of the membrane to these ions

2. Channels allow ions to diffuse across membranes Voltage-gated: Na + channels, K + channels, Ca 2+ channels Ligand-gated: neurotransmitters (acetylcholine, glutamate)

3. Figure 5-34a Potassium Equilibrium Potential

4. Figure 5-34b

5. Figure 5-34c Resting membrane potential is due mostly to high potassium permeability

6. The Nernst equation describes an ion’s equilibrium potential where: R is the gas constant (8.314 X 10 7 dyne-cm/mole degree), T is the absolute temperature in o Kelvin, z is the charge on the ion F is the Faraday (the amount of electricity required to chemically alter one gram equivalent weight of reacting material = 96,500 coulombs).

7. A simpler version of the Nernst equation At 37ºC : When ions can move across a membrane, they will bring the membrane potential to their equilibrium potential.

8. Typical ion concentrations

9. Calculating the membrane potential for a cell that is only permeable to K + [K + ] out = 5 mM [K + ] in = 150 mM E k = 61 x (-1.5) = -92 mV

10. Sodium Equilibrium Potential E Na = 61 x 1 = +61 mV

11. The Na + -K + -ATPase (“sodium pump”) works to keep intracellular K + high and Na + low

12. The membrane potential can be described by the relationship between ion permeabilities and their concentrations The Goldman equation: V m = P Na [Na + ] out + P K [K + ] out + P Cl [Cl - ] in Predicting the membrane potential (V m ) P Na [Na + ] in + P K [K + ] in + P Cl [Cl - ] out 61 log At the resting potential a. K + is very close to equilibrium. b. Na + is very far from its equilibrium. c. P K >> P Na

13. Real neurons and “Dynamic Polarization” Pyramidal cell Layer V neocortex Purkinje cell Cerebellum Axon Dendrites Santiago Ramon y Cajal, 1900 Axon collaterals Collateral branch Input Output

14. Electrical Signals: Ion Movement Resting membrane potential determined by –K + concentration gradient –Cell’s resting permeability to K +, Na +, and Cl – Gated channels control ion permeability –Mechanically gated –Ligand gated –Voltage gated

15. Current flow through ion channels leads to changes in membrane potential Ohm’s Law: V = I * R V = voltage, I = current (Amps), R = resistance (Ohms) I = V/R or I = V * G G = conductance (Siemens) For current to flow, there must be a driving force (V m - E ion ) > or < 0, thus I = (V m - E ion ) * G If current flows across a resistance--the cell membrane acts like one--there is a change in voltage (membrane potential).

16. 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. Graded Potentials

17. Graded potentials decay as they move over distance.

18. Cable theory

19. “Overshoot” mV +40 -80 0 1 ms Action Potential All-or-none Not due to “membrane breakdown” Shock

20. Na + -dependence of AP

21. Voltage-clamp

22. Voltage-clamp of squid giant axon

23. Isolation of Na and K currents

24. I/V relationship of Na and K channels

25. HH model

26. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Action Potentials Figure 8-9 (1 of 9)

27. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Action Potentials Figure 8-9 (2 of 9)

28. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Action Potentials Figure 8-9 (3 of 9)

29. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Action Potentials Figure 8-9 (4 of 9)

30. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Action Potentials Figure 8-9 (5 of 9)

31. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 8-9 (6 of 9) Electrical Signals: Action Potentials

32. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Action Potentials Figure 8-9 (7 of 9)

33. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Action Potentials Figure 8-9 (8 of 9)

34. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 8-9 (9 of 9) Electrical Signals: Action Potentials Why is AP peak < E Na ?

35. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Voltage-Gated Na + Channels Na + channels have two gates: activation and inactivation gates Figure 8-10a

36. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Voltage-Gated Na + Channels Figure 8-10c

37. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Voltage-Gated Na + Channels Figure 8-10d

38. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Refractory Period

39. Figure 8-14 How does an AP travel down an axon?

40. AP propagation

44. Figure 8-15, step 5

45. Speed of AP conduction is governed by: Diameter of the axon Resistance of the axon membrane to ion leakage

46. Myelin sheath “insulates” axons

47. Saltatory conduction

48. 1 mm Axon size matters

49. Myelination increases conduction velocity Kawasaki Z750S Top speed=170 mph Top speed=225 mph

50. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Graded Potentials Subthreshold and suprathreshold graded potentials

51. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Graded Potentials Figure 8-8b

52. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Electrical Signals: Coding for Stimulus Intensity Dendrite AP trigger zone Axon terminal

53. Patch-clamp recording Giga=10 9 Mega= 10 6 vs. sharp microelectrode Pros: high resistance seal & low resistance electrode better for recording small currents and injecting large currents Cons: disrupt (“dialyze”) cellular contents

54. Single channel recordings “stochastic behavior” Characterize channels by their: conductance (pS) selectivity kinetics

55. Whole-cell recording of different types of K channels

56. Channels are comprised of multiple subunits

57. Ligand-gated ion channels