Binding of G alpha(o) N terminus is responsible for the voltage-resistant inhibition of alpha(1A)(P/Q-type, Ca(v)2.1) Ca2+ channels

G-protein-mediated inhibition of presynaptic voltage-dependent Ca2+ channel s is comprised of voltage-dependent and -resistant components. The former i s caused by a direct interaction of Ca2+ channel alpha1 subunits with G bet a 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 th e C terminus of the alpha (1A) channel subunit, and that the binding induce s the voltage-resistant inhibition. An alpha (1A) C-terminal peptide, an an tiserum raised against G alpha (o) N terminus, and a G alpha (o) N-terminal peptide all attenuated the voltage-resistant inhibition of alpha (1A) curr ents. 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 domai n of the alpha (1B) channel showed similar ability in the binding with G al pha (o) N terminus, the above mentioned treatments were ineffective in the alpha (1B) channel current. These findings demonstrate that the voltage-res istant inhibition of the P/Q-type, alpha (1A) channel is caused by the inte raction between the C-terminal domain of Ca2+ channel alpha (1A) subunit an d the N-terminal region of G alpha (o).