2. Learning Objectives Students should be able to: Define resting membrane potential and how it is generated. Relate Nernst Equilibrium potential for sodium, potassium and chloride ion with resting membrane potential. Describe the role of leak channels and sodium potassium pump in the generation of resting membrane potential.

3. Students should be able to: Define action potential. Describe the phases of action potential. Explain the ionic basis of electrical events in an action potential and types of channels involved in it.

4. Describe the properties of action potential (all or none law) and variation in action potential in different tissues like smooth, skeletal and cardiac muscles. Illustrate difference between graded potential and action potential with the few examples (motor end plate potential, excitatory post synaptic potential, inhibitory post synaptic potential). How action potential is propagated through mylinated and unmylinated nerve fibers. What are the factors affecting the spread of conduction of action potential.

5. What is membrane potential?

6. The cell membranes of all body cells in the resting condition are, polarized which means that they show an electrical potential difference commonly used term for potential difference is only potential. Membrane potential refers to a separation of charges across the membrane or a difference in the relative number of cations and anions in the ICF and ECF.

7. RESTING MEMBRANE POTENTIAL

8. Basic Physics of Membrane Potentials Diffusion potential Is the potential difference generated across a membrane because of conc. difference of an ion It can be generated only if the membrane is permiable to the ion Diffusion potentials are created by very few ions which do not result in changes in concentration of diffusing ions

9. Equilibrium potential Is the diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a concentration difference An electrochemical equilibrium, i.e the chemical and electrical driving forces that act on an ion are equal and opposite, therefore, no net diffusion of the ion occur

12. Nernst Equation Relation of diffusion potential to the concentration difference…… resulting in Nernst (equilibrium) potential For any univalent ion at body temperature of 37° C EMF (mV)= +/-61log (Conc.inside/Conc.outside) Calculate for K + and Na + K= -61log(140/4) Na= -61log(14/142) For a positive ion you use negative and vice versa Sign shows the polarity inside the cell.

13. For potassium If K o = 4 mM and K i = 140 mM E K = -61 log(140/4) E K = -61 log(35) E K = -94 mV

14. For Sodium If Na o = 142 mM and Na i = 14 mM E K = -61 log(14/142) E K = -61 log(0.1) E K = +61 mV

15. Role of multiple ions

16. Factors Affecting RMP 3 factors Polarity of the electrical charge of each ion Membrane permeability of the ions (p) Concentrations [c] of respective ions on both sides: (i= inside), (o= outside)

18. EMF (mV)= - 86 mV

19. What is the role Na-K pump? Electrogenic pump Concentration gradient Contributes -4mV.

21. Action potential These are rapid transient changes in the membrane potential that spread rapidly along the nerve fiber membrane.

23. Graded potentials

28. Stages of Action potential

32. Afterdepolarisation: The descending limb of action potential does not reach to the baseline abbruptly, but it shows a delay of few seconds. Decrease rate of K efflux. Afterhyperpolarisation: The descending limb of action potential dips a little below the baseline of RMP. Continued K efflux.

34. Propagation of Action potential

35. Unmyelinated nerve fiber

37. Myelination

38. Myelinated nerve fiber

41. Effects of myelination High Velocity action potentials occur at the unmyelinated nodes of Ranvier that occur between the myelinated internodes Thus an action potential is propagates along the axon of a neuron at rates significantly higher than would be possible without the myelination of the axon (200 m/s compared to 2 m/s). Energy efficiency helps in reducing energy expenditure, because the amount of sodium and potassium ions that need to be pumped to bring the concentrations back to the resting state following each action potential is decreased pumped Sites Occurs only at the noded of ranvier

42. Effect of electrolytes Sodium:Decreasing the external Na + concentration reduces the size of the action potential but has little effect on the resting membrane potential. The lack of much effect on the resting membrane potential would be predicted, since the permeability of the membrane to Na + at rest is relatively low. Potassium:Conversely, increasing the external K + concentration decreases the resting membrane potential.

43. Magnitude of stimulus Sub threshold stimulus Threshold stimulus Suprathreshold stimulus

44. Magnitude of stimulus It is possible to determine the minimal intensity of stimulating current (threshold intensity) that, acting for a given duration, will just produce an action potential. Action potential fails to occur if the stimulus is subthreshold in magnitude,produces graded potentials. Suprathreshold stimuli produce action potential during relative refractory period.

46. Refractory period

49. "All-or-None" Law The action potential fails to occur if the stimulus is subthreshold in magnitude, and it occurs with constant amplitude and form regardless of the strength of the stimulus if the stimulus is at or above threshold intensity. The action potential is therefore "all or none" in character and is said to obey the all-or- none law.

50. Cardiac muscles

51. Plateau greatly prolongs the period of depolarization. This type of action potential with plateau is seen in heart muscle fibers.

52. Opening of fast channels causes the spike portion of the action potential. The slow, prolonged opening of the slow calcium- sodium channels mainly allows calcium ions to enter the fiber. This is largely responsible for the plateau portion of the action potential.

54. Smooth muscles

55. Sensitive to stretch Slow wave potential Spike potential

57. Inhibition of excitability Stabilizers - Membrane stabilizing factors decrease excitability High extracellular fluid calcium ion conc. Decrease membrane permiability to sodium ions & simulteneously reduces excitability Local anaesthetics Procaine & tetracaine Acts directly on sodium channel activation gates Making it much more difficult for the gates to open

58. Membrane potential & action potentials Are recorded by cathode Ray Oscilloscope

59. s