Gating kinetics of the alpha 1I 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-chan nels. We have examined the underlying mechanisms using whole-cell recording s from rat all stably expressed in HEK293 cells. We found several kinetic d ifferences between alpha 1G and all, including some properties that at firs t appear qualitatively different. Notably, all tail currents require two or even three exponentials, whereas alpha 1G tails were well described by a s ingle exponential over a wide voltage range. Also, closed-state inactivatio n is more significant for all, even for relatively strong depolarizations. Despite these differences, gating of all can be described by the same kinet ic scheme used for alpha 1G, where voltage sensor movement is allostericall y coupled to inactivation. Nearly all of the rate constants in the model ar e 5-12-fold slower for alpha 1I, but the microscopic rate for channel closi ng is fourfold faster. This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability.