Lecture 2

• From the Goldman equation, Em can be calculated and is about -70 mV
• Under certain circumstances, the permeability of Na+ can be dominant and much more than then K+ ion and MP can change drastically

  
• If the membrane properties change to make the membrane most permeable to Na+, then there is a net Na+ current inward

  
• At equilibrium, there is a net cation accumulation inside the membrane
• Membrane potential is positive inside with respect to the outside: ENa+ = +60 mV
• Inside the cell, we have large proteins (which are basically trapped, they can only get across to the outside using exocitosis), and since they tend to have "-" charges, the Cl- ion is pushed out of the cell
• Therefore, the Cl- ions tend to be more concentrated on the outside in the extracellualr space
• This is due to anion proteins present on the inside and not due to active pump
• To generate a signal, membrane increases its conductance by opening a channel permeable only to Na+ ion
• This is a voltage-gated Na+ channel
• In normal resting MP, this Na+ channel is shut!
• To open this Na+ channel we need to depolarize (removing the polarization) the membrane by a certain amount
• This Na+ channel is normally closed at -70 mV
• This Na+ channel is only opened by depolarizing the membrane to a threshold potential of about -55 mV
• Na+ channel inactivation then takes place
• To remove inactivation, the MP needs to fall below threshold again
• An AP is essentially an impulse, a very short lived, change in the MP, an AP is used as a signal
• You can only produce an AP in membrane that contains the voltage-gated Na+ channels
• By definition, the presence of voltage-gated Na+ channel makes the membrane 'excitable'
• Na+ channels occur in high density within 'excitable' membranes
• When channels are open, membrane potential surges towards ENa+ = 60 mV
• But channels rapidly inactivate (1/2 ms)
• Na+ inactivation leaves K+ leakage as main current, and resting potential is restored
• Minimum depolarization necessary to induce the regenerative mechanism for the opening of Na+ channels
• Action potential from threshold and supra-threshold stimulus have the same magnitude
• Information pertaining to stimulus intensity is coded by the changes in the frequency of the Action Potential
• After we generate an AP and inactivate the Na+ channels, we have a period in which all or some Na+ channels are inactivated
• Na+ channels remain inactivated until membrane potential drops below 'threshold', then channels reconfigure to their original state and membrane becomes excitable again
• Absolute RP: none of channels are reconfigured
• Relative RP: some but not all of channels are reconfigured (generally 2-5 ms duration)
• You could completely block the membrane from producing an AP, but how?
• Keep the membrane depolarized! (remember that in order to generate an AP, we need to repolarize the membrane to below threshold level to reconfigure the Na+ channels to its original state)
• If you permanently depolarize the membrane, keep it at 20 mV (above threshold), the Na+ channels will be permanently inactivated, and you will not be able to generate another AP
• You just need to destroy the concentration gradient for K+ (remember that K+ current is responsible for keeping the MP polarized to -70 mV)
• Introduce more K+ in the extracellualr space (excess [K+]o — e.g. with KCl injection)
• This will result in permanent Na+ inactivation and the membrane will remain in absolute refractory state and the membrane becomes in-excitable

  
• You want this channel to act at a later phase to bring MP back down to resting levels (remember that K+ channels are needed to repolarize the membrane)
• Due to the presence of this "extra" K+ channels, in conjunction with the leakage K+ channels, we have much greater outward K+ current
• This results in the MP to be more polarized than normal
• Thus, the voltage-gated K+ channels cause a hyperpolarization after the AP