Fast Inactivation of CaV2.2 Channels Is Prevented by the Gβ1 Subunit in Rat Sympathetic Neurons.

Voltage-dependent regulation of CaV2.2 channels by G-proteins is performed by the β (Gβ) subunit. Most studies of regulation by G-proteins have focused on channel activation; however, little is known regarding channel inactivation. This study investigated inactivation of CaV2.2 channels in superior cervical ganglion neurons that overexpressed Gβ subunits. CaV2.2 currents were recorded by whole-cell patch clamping configuration. We found that the Gβ1 subunit reduced inactivation, while Gβ5 subunit did not alter at all inactivation kinetics compared to control recordings. CaV2.2 current decay in control neurons consisted of both fast and slow inactivation; however, Gβ1-overexpressing neurons displayed only the slow inactivation. Fast inactivation was restored by a strong depolarization of Gβ1-overexpressing neurons, therefore, through a voltage-dependent mechanism. The Gβ1 subunit shifted the voltage dependence of inactivation to more positive voltages and reduced the fraction of CaV2.2 channels resting in the inactivated state. These results support that the Gβ1 subunit inhibits the fast inactivation of CaV2.2 channels in SCG neurons. They explain the long-observed sustained Ca2+ current under G-protein modulation.