Preferential closed-state inactivation of neuronal calcium channels

Parag G. Patil, David L. Brody, David T. Yue

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1027-1038
Number of pages12
Issue number5
StatePublished - May 1998
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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