Regulators of G protein signaling proteins as determinants of the rate of desensitization of presynaptic calcium channels

Norepinephrine inhibits ω-conotoxin GVIA-sensitive presynaptic Ca²⁺ channels in chick dorsal root ganglion neurons through two pathways, one mediated by GO and the other by G(i). These pathways desensitize at different rates. We have found that recombinant Gα interacting protein (GAIP) and regulators of G protein signaling (RGS)4 selectively accelerate the rate of desensitization of G(o)- and G(i)-mediated pathways, respectively. Blockade of endogenous RGS proteins using antibodies raised against Gα interacting protein and RGS4 slows the rate of desensitization of these pathways in a selective manner. These results demonstrate that different RGS proteins may interact with G(i) and G(o) selectively, giving rise to distinct time courses of transmitter-mediated effects.