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 appare...

Full description

Saved in:
Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 1998-05, Vol.20 (5), p.1027-1038
Main Authors: Patil, Parag G, Brody, David L, Yue, David T
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Calcium Channels - chemistry
Calcium Channels - physiology
Calcium Channels, L-Type
Calcium Channels, N-Type
Electrophysiology
GTP-Binding Proteins - physiology
Humans
Ion Channel Gating - physiology
Nerve Tissue Proteins - physiology
Neurons - chemistry
Neurons - physiology
Patch-Clamp Techniques
Protein Conformation
Rabbits
Rats
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Ca 2+ entry during a train of APs.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(00)80483-3