Preferential closed-state inactivation of neuronal calcium channels.
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
P G
PG
Program in Molecular and Cellular Physiology, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Brody
D L
DL
Yue
D T
DT
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000737:chemistry* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D019204:GTP-Binding Proteins; D009419:Nerve Tissue Proteins