Gating Kinetics of the {alpha}1i T-Type Calcium Channel

doi:10.1085/jgp.118.5.457

Scientifica: Experts in Electrophysiology

Published 1 November 2001. doi:10.1085/jgp.118.5.457

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Original Article

Gating Kinetics of the ${alpha}$ 1i T-Type Calcium Channel

Charles J. Frazier^a, Jose R. Serrano^a, Eric G. George^a, Xiaofeng Yu^a, Ahalya Viswanathan^a, Edward Perez-Reyes^b, and Stephen W. Jones^a

^a Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106
^b Department of Pharmacology, University of Virginia, Charlottesville, VA 22908
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106.(216) 368-3952

swj{at}po.cwru.edu

The ${alpha}$ 1I T-type calcium channel inactivates almost 10-fold moreslowly than the other family members ( ${alpha}$ 1G and ${alpha}$ 1H) or most nativeT-channels. We have examined the underlying mechanisms usingwhole-cell recordings from rat ${alpha}$ 1I stably expressed in HEK293cells. We found several kinetic differences between ${alpha}$ 1G and ${alpha}$ 1I,including some properties that at first appear qualitativelydifferent. Notably, ${alpha}$ 1I tail currents require two or even threeexponentials, whereas ${alpha}$ 1G tails were well described by a singleexponential over a wide voltage range. Also, closed-state inactivationis more significant for ${alpha}$ 1I, even for relatively strong depolarizations.Despite these differences, gating of ${alpha}$ 1I can be described bythe same kinetic scheme used for ${alpha}$ 1G, where voltage sensor movementis allosterically coupled to inactivation. Nearly all of therate constants in the model are 5–12-fold slower for ${alpha}$ 1I,but the microscopic rate for channel closing is fourfold faster.This suggests that T-channels share a common gating mechanism,but with considerable quantitative variability.

Key Words: inactivation • activation • T-current • LVA channel • kinetic models

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