Ca(2+)-dependent inactivation of the class C L-type Ca2+ channel is a property of the alpha 1 subunit.

The stably expressed Ca2+ channel alpha 1C-a and alpha 1C-b subunit were used to investigate the molecular basis for Ca(2+)-dependent inactivation of the L-type current. The Ba2+ current (IBa) of both channels had similar kinetics and inactivated with one time constant of about 400 ms at +20 mV, whereas the Ca2+ current (ICa) could be fitted only with a bi-exponential function. The fast (tau f) and the slow (tau s) time constant were about 20 ms and 400 ms, respectively. The inactivation of ICa strongly depended on the entry of Ca2+ as shown by prepulses and variation of the intracellular Ca2+ chelator. Coexpression of the alpha 1C subunits with the auxiliary alpha 2/delta and beta subunits accelerated the voltage-dependent but not the Ca(2+)-dependent inactivation of the channels. These results suggest that the alpha 1C subunit of L-type Ca2+ channels itself mediates the Ca(2+)-dependent inactivation of the current.