CHAPTER 5 Generation and Conduction of Action Potentials •Fig. 5.6 A, Amicropipetteisappliedtothecellmembraneandsufficientsuctionisappliedtoelectricallyisolateasinglechannelatthetip.Anamplifierrecordsthecurrentthatpassesthroughthechannel.B, EachlineshowsthecurrentpassedthroughaK+ channelasitopensspontaneously.Notethatasthetransmembranevoltageisprogressivelydepolarized(fromtoptobottom),boththeprobabilitythatthechannelwillopenandtheamplitudeofthecurrentareincreased.C, Agraphoftheprobabilitythatthechannelwillopenversusmembranedepolarization.D, Agraphoftransmembranevoltage(lowertracing,right-sidedscale)andthecurrentdensityfromapopulationofNa+ channels(uppertracing,left-sidedscale)isolatedinapatchsimilartothatinA (exceptthatitcontainsseveralNa+ channels).Initially,atrestingpotential,thereisnocurrentflow.Withdepolarizationto0mV,thereisaninwardNa+ currentthatiscurtailedevenwhilethedepolarizationcontinues.Thisisduetotheclosingofthechannels’inactivationgates.Afterabriefreturntorestingpotential,anotherdepolarizationto0mVevokesinwardcurrentflow,butitissmallerandbrieferbecausetherehasnotbeenenoughtimeformostoftheslowinactivationgatestoreopen.(B, C, andD areredrawnfrom http://www.physiologymodels.info/electrophysiology voltage-sensitive gate (activation gate) whose probability of being open increases with depolarization. However, unlike K+ channels, with maintained depolarization, Na+ channels open only at the onset of the depolarization and then remain closed. This suggests that Na+ channels have a second gate (inactivation gate) whose probability of being open goes down as the membrane is depolarized. Thus any Na+ current conducted by these channels will be transient (see
Fig. 5.6D ), because the same stimulus (depolarization) increases both the probabilities that the activation gate will open and that the inactivation gate will close. Note that the Na+ channel thus has two closed states, one in which the activation gate is closed, and the channel is said to be “closed,” and one in which the inactivation gate is closed, and the channel is referred to as “inactivated.” The reason the channel is called “inactivated” when the second gate closes is that once this gate closes, it will remain so until the membrane is repolarized. The activation gate, in contrast, can open and close at all membrane potentials, just with differing probabilities.
With the knowledge of the Na+ and K+ channel gating behavior just discussed, we can understand how the action potential is generated by the interaction of these channels (in the following, we assume that both gNa and gK change during the action potential). As stated previously, the action potential starts with a rapid increase in Na+ conductance (gNa;
Fig. 5.7 ). This increase in Na+ conductance reflects the opening of many Na+ channels in response to the depolarization. The open channels allow the influx of Na+ ions, and the effect of this current is to depolarize the membrane further. Note that this is a positive feedback loop, which accounts for the explosive nature of the action potential: the Na+ current depolarizes the membrane, which causes more Na+ channels to open, which in turn increases the Na+ current. In sum, the voltage-dependent opening of Na+ channels and the depolarizing action of the Na+ current account for the rising phase of the action potential.