Effects of the dihydropyridine receptor subunits gamma and alpha(2)delta on the kinetics of heterologously expressed L-type Ca2+ channels

Ba2+ currents through L-type Ca2+ channels were measured in tsA201 cells tr ansiently transfected with expression vectors encoding the dihydropyridine (DHP) receptor subunits alpha(1C), beta(1a)-GFP, alpha(2)delta and gamma. T he subunit effect on channel function was studied by omitting either alpha( 2)delta or gamma from the transfection mixture and analyzing the voltage de pendence and kinetics of activation, inactivation and recovery from inactiv ation. Activation could be described by a single exponential function while the time course of inactivation of the Ba2+ current followed a double expo nential function. Progressively longer depolarization led to increasingly s lower recovery, indicating the successive occupancy of several inactive sta tes. Activation parameters remained largely unaffected in gamma-deficient c ells whereas the voltage dependence of inactivation was shifted by 16 mV to more positive potentials and the larger one of the two inactivation time c onstants was increased by one-third. On the other hand, alpha(2)delta-defic ient cells showed decreased current density and slowed activation and inact ivation. Recovery from inactivation was significantly slowed by gamma coexp ression. This and the effect of the gamma subunit on steady-state inactivat ion were independent of the presence of alpha(2)delta. We conclude that gam ma stabilizes L-type Ca2+ channel inactivation in a way similar to certain Ca2+-antagonistic drugs. alpha(2)delta is not needed for this effect.