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

Norepinephrine inhibits omega-conotoxin GVIA-sensitive presynaptic Ca2+ cha nnels in chick dorsal root ganglion neurons through two pathways, one media ted by G(o) and the other by G(i). These pathways desensitize at different rates. We have found that recombinant G alpha interacting protein (GAIP) an d regulators of G protein signaling (RGS)4 selectively accelerate the rate of desensitization of G(o)- and G(i)-mediated pathways, respectively. Block ade of endogenous RGS proteins using antibodies raised against G alpha inte racting protein and RGS4 slows the rate of desensitization of these pathway s in a selective manner. These results demonstrate that different RGS prote ins may interact with G(i) and G(o) selectively, giving rise to distinct ti me courses of transmitter-mediated effects.