Calcium channel beta subunit promotes voltage-dependent modulation of alpha 1B by G beta gamma

Voltage-dependent calcium channels (VDCCs) are heteromultimers composed of a pore-forming alpha 1 subunit and auxiliary subunits, including the intrac ellular beta subunit, which has a strong influence on the channel propertie s. Voltage-dependent inhibitory modulation of neuronal VDCCs occurs primari ly by activation of G-proteins and elevation of the free G beta gamma dimer concentration. Here we have examined the interaction between the regulatio n of N-type (alpha 1B) channels by their beta subunits and by G beta gamma dimers, heterologously expressed in COS-7 cells. In contrast to previous st udies suggesting antagonism of G protein inhibition by the VDCC beta subuni t, we found a significantly larger G beta gamma-dependent inhibition of alp ha 1B channel activation when the VDCC alpha 1B and beta subunits were coex pressed. In the absence of coexpressed VDCC beta subunit, the G beta gamma dimers, either expressed tonically or elevated via receptor activation, did not produce the expected features of voltage-dependent G protein modulatio n of N-type channels, including slowed activation and prepulse facilitation , while VDCC beta subunit coexpression restored all of the hallmarks of G b eta gamma modulation. These results suggest that the VDCC beta subunit must be present for G beta gamma to induce voltage-dependent modulation of N-ty pe calcium channels.