Neuronal N-, P/Q-, and R-type calcium channels inactivate profoundly during a train of action potential waveforms via a voltage-dependent mechanism from intermediate closed states.
Neuronal calcium channels undergo preferential closed-state inactivation during action potential trains, which could produce widely variable depression of calcium entry.
We have investigated the inactivation mechanism of neuronal N-, P/Q-, and R-type calcium channels. Although channels inactivate slowly during square-pulse depolarization, as observed previously, we now find that they inactivate profoundly during a train of action potential (AP) waveforms. The apparent paradox arises from a voltage-dependent mechanism in which channels inactivate preferentially from intermediate closed states along the activation pathway. Inactivation can therefore extend beyond the brief duration of AP waveforms to continue between spikes, as the channel undergoes repetitive cycles of activation and deactivation. The extent of inactivation during a train is strongly affected by the subunit composition of channels. Preferential closed-state inactivation of neuronal calcium channels could produce widely variable depression of Ca2+ entry during a train of APs.
Patil et al. (1998) studied this question. Action potential (AP) waveforms vs. Square-pulse depolarization was evaluated on Inactivation mechanism of neuronal calcium channels. Neuronal N-, P/Q-, and R-type calcium channels inactivate profoundly during a train of action potential waveforms via a voltage-dependent mechanism from intermediate closed states.