Ca2+-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 Ca2+ dependent inactivation of the L-type current. The Ba2+ current (I-Ba) of both channels had similar kinetics and inactivated with one time constant of about 400 ms at + 20 mV whereas the Ca2+ current (I-Ca) 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 I-Ca 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 Ca2+-dependent inactivation of the channels. These results suggest that the alpha(1C) subunit of L-type Ca2+ channels itself mediates the Ca2+-dependent inactivation of the current.