Binding of Gαo N terminus is responsible for the voltage-resistant inhibition of α1A(P/Q-type, Cav2.1) Ca2+ channels

G-protein-mediated inhibition of presynaptic voltage-dependent Ca2+ channels is comprised of voltage-dependent and -resistant components. The former is caused by a direct interaction of Ca2+ channel alpha1 subunits with G beta gamma, whereas the latter has not been characterized well. Here, we show that the N terminus of G alpha (o), is critical for the interaction with the C terminus of the alpha (1A) channel subunit, and that the binding induces the voltage-resistant inhibition. An alpha (1A) C-terminal peptide, an antiserum raised against G alpha (o) N terminus, and a G alpha (o) N-terminal peptide all attenuated the voltage-resistant inhibition of alpha (1A) currents. Furthermore, the N terminus of G alpha (o) bound to the C terminus of alpha (1A) in vitro, which was prevented either by the alpha (1A) channel C-terminal or G alpha (o) N-terminal peptide. Although the C-terminal domain of the alpha (1B) channel showed similar ability in the binding with G alpha (o) N terminus, the above mentioned treatments were ineffective in the alpha (1B) channel current. These findings demonstrate that the voltage-resistant inhibition of the P/Q-type, alpha (1A) channel is caused by the interaction between the C-terminal domain of Ca2+ channel alpha (1A) subunit and the N-terminal region of G alpha (o).