Gating kinetics of the α1I T-type calcium channel

The alpha 11 T-type calcium channel inactivates almost 10-fold more slowly than the other family members (alpha 1G and alpha 1H) or most native T-channels. We have examined the underlying mechanisms using whole-cell recordings from rat all stably expressed in HEK293 cells. We found several kinetic differences between alpha 1G and all, including some properties that at first appear qualitatively different. Notably, all tail currents require two or even three exponentials, whereas alpha 1G tails were well described by a single exponential over a wide voltage range. Also, closed-state inactivation is more significant for all, even for relatively strong depolarizations. Despite these differences, gating of all can be described by the same kinetic scheme used for alpha 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 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.