Fast Inactivation of Ca2.2 Channels Is Prevented by the Gβ Subunit in Rat Sympathetic Neurons.

Voltage-dependent regulation of Ca2.2 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 Ca2.2 channels in superior cervical ganglion neurons that overexpressed Gβ subunits. Ca2.2 currents were recorded by whole-cell patch clamping configuration. We found that the Gβ subunit reduced inactivation, while Gβ subunit did not alter at all inactivation kinetics compared to control recordings. Ca2.2 current decay in control neurons consisted of both fast and slow inactivation; however, Gβ-overexpressing neurons displayed only the slow inactivation. Fast inactivation was restored by a strong depolarization of Gβ-overexpressing neurons, therefore, through a voltage-dependent mechanism. The Gβ subunit shifted the voltage dependence of inactivation to more positive voltages and reduced the fraction of Ca2.2 channels resting in the inactivated state. These results support that the Gβ subunit inhibits the fast inactivation of Ca2.2 channels in SCG neurons. They explain the long-observed sustained Ca current under G-protein modulation.