Calcium Channel b Subunit Promotes Voltage-Dependent Modulation of a1B by Gbg

Voltage-dependent calcium channels (VDCCs) are heteromultimers composed of a pore-forming a1 subunit and auxiliary subunits, including the intracellular b 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 Gbg dimer concentration. Here we have examined the interaction between the regulation of N-type (a1B) channels by their b subunits and by Gbg dimers, heterologously expressed in COS-7 cells. In contrast to previous studies suggesting antagonism of G protein inhibition by the VDCC b subunit, we found a significantly larger Gbg-dependent inhibition of a1B channel activation when the VDCC a1B and b subunits were coexpressed. In the absence of coexpressed VDCC b subunit, the Gbg 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 b subunit coexpression restored all of the hallmarks of Gbg modulation. These results suggest that the VDCC b subunit must be present for Gbg to induce voltage-dependent modulation of N-type calcium channels.