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Original Article |
1i T-Type Calcium Channel
swj{at}po.cwru.edu
The
1I T-type calcium channel inactivates almost 10-fold more slowly than the other family members (1G and 1H) or most native T-channels. We have examined the underlying mechanisms using whole-cell recordings from rat 1I stably expressed in HEK293 cells. We found several kinetic differences between 1G and 1I, including some properties that at first appear qualitatively different. Notably, 1I tail currents require two or even three exponentials, whereas 1G tails were well described by a single exponential over a wide voltage range. Also, closed-state inactivation is more significant for 1I, even for relatively strong depolarizations. Despite these differences, gating of 1I can be described by the same kinetic scheme used for 1G, where voltage sensor movement is allosterically coupled to inactivation. Nearly all of the rate constants in the model are 5–12-fold slower for 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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