Voltage-dependent facilitation of cardiac L-type Ca channels expressed in HEK-293 cells requires β-subunit

The activity of native L-type Ca channels can be facilitated by strong depolarizations. The cardiac Ca channel α₁(C)-subunit was transiently expressed in human embryonic kidney (HEK-293) cells, but these channels did not exhibit voltage-dependent facilitation. Coexpression of the Ca channel β(1a)- or β(2a)-subunit with the α(1C)-subunit enabled voltage-dependent facilitation in 40% of cells tested. The onset of facilitation in α(1C) + β(1a)-expressing HEK-293 cells was rapid after a depolarization to + 100 mV (τ = 7.0 ms). The kinetic features of the facilitated currents were comparable to those observed for voltage-dependent relief of G protein inhibition demonstrated for many neuronal Ca channels; however, intracellular dialysis with guanosine 5'-O-(2-thiodiphosphate) and guanosine 5'-O-(3- thiotriphosphate) in the patch pipette had no effect on facilitation. Stimulation of G protein-coupled receptors, either endogenous (somatostatin receptors) or coexpressed (adenosine A₁ receptors), did not affect voltage- dependent facilitation. These results indicate that the cardiac Ca channel α(1C)-subunit can exhibit voltage-dependent facilitation in HEK-293 cells only when coexpressed with an auxiliary β-subunit and that this facilitation is independent of G protein pathways.