Calcium Channel β Subunit Promotes Voltage-Dependent Modulation of α1B by G βγ

Abstract

Voltage-dependent calcium channels (VDCCs) are heteromultimers composed of a pore-forming α1 subunit and auxiliary subunits, including the intracellular β subunit, which has a strong influence on the channel properties. Voltage-dependent inhibitory modulation of neuronal VDCCs occurs primarily by activation of G-proteins and elevation of the free G βγ dimer concentration. Here we have examined the interaction between the regulation of N-type ( α1B) channels by their β subunits and by G βγ dimers, heterologously expressed in COS-7 cells. In contrast to previous studies suggesting antagonism of G protein inhibition by the VDCC β subunit, we found a significantly larger G βγ-dependent inhibition of α1B channel activation when the VDCC α1B and β subunits were coexpressed. In the absence of coexpressed VDCC β subunit, the G βγ dimers, either expressed tonically or elevated via receptor activation, did not produce the expected features of voltage-dependent G protein modulation of N-type channels, including slowed activation and prepulse facilitation, while VDCC β subunit coexpression restored all of the hallmarks of G βγ modulation. These results suggest that the VDCC β subunit must be present for G βγ to induce voltage-dependent modulation of N-type calcium channels.