Resting Membrane Potential

1. Resting Membrane Potential • Membrane potential at which neuron membrane is at rest, ie does not fire action potential • Written as Vr

2. Ionic Equilibrium Potential • Membrane Potential (potential difference across the plasma membrane) at which the net flow of an ion type = zero • The number of ions moving into the cell = the number of ions moving out of the cell for a particular species of ion

3. Nernst Equation Variables • Assumes that membrane is permeable to that ion • As temperature increases the diffusion increases • As charge on the molecule increases, it decreases the potential differences needed to balance diffusion forces.

4. Simplified Eion (at 37°C) • Eion = 2.303 RT/zF log [ion]o/[ion]in • Ena = 61.54mV log [Na]o/[Na]I = 62 mV • EK = 61.54mV log [K]o/[K]I = -80 mV • ECa = 30.77mV log [Ca]o/[Ca]I = 123 mV • CCl = -61.54mV log [Cl]o/[Cl]I = - 65 mV

7. Goldman Equation • Vr= RT/F ln Pk[K]o+Pna[Na]o+PCl[Cl]i Pk[K]I+Pna[Na]I+PCl[Cl]o Also known as the constant field equation because it assumes that electrical field of the membrane potential is equal across the span of the membrane

8. Membrane Permeability • Membrane is 50 more permeable to K than to Na • Pk/Pna = 50 • PCl/Pk = 0 • The membrane is so impermeable to Chloride that you drop it from the equation

9. Goldman Equation • Vr= RT/F ln Pk[K]o+ Pna[Na]o+ PCl[Cl]i • Pk[K]I+ Pna[Na]I+ PCl[Cl]o • Eion = 2.303 RT/zF log Pk[K]o+Pna[Na]o Pk[K]I+Pna[Na]I • Vr= 61.54 mV log 50[5]o +1[150]o 50[100]i+1[15]I • = - 65mV

11. Not to study • Donnans equilibrium • Osmolarity considerations

12. Action Potential Changes in Ion Permeability allows inward Na flux and triggers an increased outward K flux through voltage gated ion channels Causes transient change in Membrane Potential The change in ion permeability is triggered by transient depolarization of the membrane

16. Conductance = g • How many charges (ions) enters or leaves cell (inverse of resistance) • due to: • number of channels/membrane area • Highest density at axon hillock • number of open channels • ion concentration on either side of membrane • Measured in Siemens (S), in cells pS (pico; -12)

18. Hodgkin and Huxley won Nobel Prize for Voltage clamp in 1961 used to identify the ion species that flowed during action potential Clamped Vm at 0mv to remove electric driving force than varied external ion concentration and observed ion efflux during a voltage step Sakman and Nehr won Nobel Prize for Patch Clamp in 1991 measured ion flow through individual channels shows that each channel is either in open or closed configuration with no intermediate. The sum of many recordings gives you the shape of sodium conductance. Historical Figures

19. Information Coding • Is NOT in shape of action potential • Is in the action potential frequency of firing —how many are triggered • In the action potentials pattern or timing of propagation

20. Conductance = g • How many charges (ions) enters or leaves cell (inverse of resistance) • due to: • number of channels/membrane area • Highest density at axon hillock • number of open channels • ion concentration on either side of membrane • Measured in Siemens (S), in cells pS (pico; -12)

23. Generation of Resting Membrane Potential (-70mV) • Plasma membrane • Selective permeability, permeable to K, not Na • Unequal distribution of ions across membrane • Due to open potassium channels and closed sodium and chloride channels • Action of ion pumps 3Na/2K ATPase

25. Ionic Equilibrium Potential • The membrane potential that balances the ions concentration gradient so that there is no net current for that ion. • No permeability factor.

26. Equilibrium Potential of An Ion • The membrane potential at which the net driving force propelling the ion in = the net driving force propelling the ion out. • Written Eion; ENa, ECl, EK

29. Nernst Equation • Eion = 2.303 RT/zF log [ion]o/[ion]in • Eion = ionic equilibrium potential • Z= charge of ion • F= Faraday’s constant • T= absolute temperature (0Kelvin/-273°C) • R= gas constant

30. Action Potential: a transient and rapid sequence of changes in the membrane potential Action Potentials Can travel up to 100 meters/second Usually 10-20 m/s 0.1sec delay between muscle and sensory neuron action potential

31. Membrane Permeability • Membrane is 50 more permeable to K than to Na • Pk/Pna = 50 • PCl/Pk = 0 • The membrane is so impermeable to Chloride that you drop it from the equation

32. Goldman Equation • Vr= RT/F ln Pk[K]o+ Pna[Na]o+ PCl[Cl]i • Pk[K]I+ Pna[Na]I+ PCl[Cl]o • Eion = 2.303 RT/zF log Pk[K]o+Pna[Na]o Pk[K]I+Pna[Na]I • Vr= 61.54 mV log 50[5]o +1[150]o 50[100]i+1[15]I • = - 65mV

34. Ion Permeability • Changes during action potential • The plasma membrane becomes permeable to sodium ions • Permeability increases from 0.02 to 20=1000 fold increase • Causes Em aka Vr to approach Ena at positive voltages = +20mV

35. overshoot Falling rising undershoot

36. 6 Characteristics of an Action Potential • #1 Triggered by depolarization • a less negative membrane potential that occurs transiently • Understand depolarization, repolarization and hyperpolarization

37. #2 Threshold • Threshold depolarization needed to trigger the action potential • 10-20 mV depolarization must occur to trigger action potential

38. #3 All or None • Are all-or- none event • Amplitude of AP is the same regardless of whether the depolarizing event was weak (+20mV) or strong (+40mV).

39. #4 No Change in Size The shape (amplitude & time) of the action potential does not change as it travels along the axon • Propagates without decrement along axon

40. #5 Reverses Polarity • At peak of action potential the membrane potential reverses polarity • Becomes positive inside as predicted by the Ena Called OVERSHOOT • Return to membrane potential to a more negative potential than at rest • Called UNDERSHOOT

41. #6 Refractory Period • Absolute refractory period follows an action potential. Lasts 1 msec • During this time another action potential CANNOT be fired even if there is a transient depolarization. • Limits firing rate to 1000AP/sec

42. Stimulating electrode: Introduces current that can depolarize or hyper-polarize Recording electrode: Records change in Potential of the membrane At a distance away

43. At Threshold Na influx equals K efflux Voltage (mVolts) along Y axis Time (msec)

45. Voltage Sensitive Ion Channels • Sodium • Potassium

46. Ionic Equilibrium Potential • Membrane Potential (potential difference across the plasma membrane) at which the net flow of an ion type = zero • The number of ions moving into the cell = the number of ions moving out of the cell for a particular species of ion

47. Regenerative Process: Once one Na channel Opens, Na enters, Depolarizes membrane, More and more Na Channels open leading to More sodium influx & causes upward & depolarizing (more +) phase of the AP

48. What does a sodium Channel look like? It is one large protein With 4 domains that Each loop through the Plasma membrane 7 Times.

49. Property of Voltage Dependent Sodium Channel • Sodium channel opens for 1-2 millisecond following threshold depolarization • then inactivates and does not open even if Vm is depolarized. • This is called sodium channel inactivation and contributes to the repolarization of Vm

50. Na Channel Gates • M gate= activation gate on Na channel; opens quickly when membrane is depolarized • H gate- inactivation gate on Na channel; Closes slowly after membrane is depolarized • causes the absolute refractory period for AP propagation