Ca2+‐dependent inactivation of the class C L‐type Ca2+ channel is a property of the α1 subunit

Abstract

The stably expressed Ca²⁺ channel α _1C-a and α _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 (τ _f) and the slow (τ _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 α _1C subunits with the auxiliary α ₂/δ and β subunits accelerated the voltage-dependent but not the Ca²⁺-dependent inactivation of the channels. These results suggest that the α _1C unit of L-type Ca²⁺ channels itself mediates the Ca²⁺-dependent inactivation of the current.