Calcium Channel β Subunits Differentially Regulate the Inhibition of N-type Channels by Individual Gβ Isoforms
Journal of Biological Chemistry
The direct inhibition of N-and P/Q-type calcium channels by G protein ␤␥ subunits is considered a key mechanism for regulating presynaptic calcium levels. We have recently reported that a number of features associated with this G protein inhibition are dependent on the G protein ␤ subunit isoform (Arnot, M. I.). Here, we have examined the abilities of different types of ancillary calcium channel ␤ subunits to modulate the inhibition of ␣ 1B N-type calcium channels by the five known different G␤
... subunit subtypes. Our data reveal that the degree of inhibition by a particular G␤ subunit is strongly dependent on the specific calcium channel ␤ subunit, with N-type channels containing the ␤ 4 subunit being less susceptible to G␤␥-induced inhibition. The calcium channel ␤ 2a subunit uniquely slows the kinetics of recovery from G protein inhibition, in addition to mediating a dramatic enhancement of the G protein-induced kinetic slowing. For G␤ 3 -mediated inhibition, the latter effect is reduced following site-directed mutagenesis of two palmitoylation sites in the ␤ 2a N-terminal region, suggesting that the unique membrane tethering of this subunit serves to modulate G protein inhibition of N-type calcium channels. Taken together, our data suggest that the nature of the calcium channel ␤ subunit present is an important determinant of G protein inhibition of N-type channels, thereby providing a possible mechanism by which the cellular/subcellular expression pattern of the four calcium channel ␤ subunits may regulate the G protein sensitivity of N-type channels expressed at different loci throughout the brain and possibly within a neuron.