Effects of the dihydropyridine receptor subunits γ and α2δ on the kinetics of heterologously expressed L-type Ca2+ channels
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Ba2+ currents through L-type Ca2+ channels were measured in tsA201 cells transiently transfected with expression vectors encoding the dihydropyridine (DHP) receptor subunits α1C, β1a-GFP, α2δ and γ. The subunit effect on channel function was studied by omitting either α2δ or γ from the transfection mixture and analyzing the voltage dependence and kinetics of activation, inactivation and recovery from inactivation. Activation could be described by a single exponential function while the time course of inactivation of the Ba2+ current followed a double exponential function. Progressively longer depolarization led to increasingly slower recovery, indicating the successive occupancy of several inactive states. Activation parameters remained largely unaffected in γ-deficient cells whereas the voltage dependence of inactivation was shifted by 16 mV to more positive potentials and the larger one of the two inactivation time constants was increased by one-third. On the other hand, α2δ-deficient cells showed decreased current density and slowed activation and inactivation. Recovery from inactivation was significantly slowed by γ coexpression. This and the effect of the γ subunit on steady-state inactivation were independent of the presence of α2δ. We conclude that γ stabilizes L-type Ca2+ channel inactivation in a way similar to certain Ca2+-antagonistic drugs. α2δ is not needed for this effect.
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