Differential interactions of the C terminus and the cytoplasmic I-II loop of neuronal Ca2+ channels with G-protein α and βγ subunits -: I.: Molecular determination

Interactions of G-protein a (G alpha) and beta gamma subunits (G beta gamma) with N- (alpha(1B)) and P/Q-type (alpha(1A)) Ca2+ channels were investigated using the Xenopus oocyte expression system. G(i3)alpha was found to inhibit both N- and P/Q-type channels by receptor agonists, whereas G beta(1)gamma(2) was responsible for prepulse facilitation of N-type channels. L-type channels (alpha(1C)) were not regulated by G alpha or G beta gamma. For N-type, prepulse facilitation mediated via G beta gamma was impaired when the cytoplasmic I-II loop (loop 1) was deleted or replaced with the alpha(1C) loop 1. G alpha-mediated inhibitions were also impaired by substitution of the alpha(1C) loop 1, but only when the C terminus was deleted. For P/Q type, by contrast, deletion of the C terminus alone diminished G alpha-mediated inhibition. Moreover, a chimera of L-type with the alpha(1B) loop 1 gained G beta gamma-dependent ent facilitation, whereas an L type chimera with the Nor P/Q-type C terminus gained G alpha-mediated inhibition. These findings provide evidence that loop 1 of N-type channels is a regulatory site for G beta gamma and the C termini of P/Q- and N-types for G alpha.