[Binding of G alpha o N-terminus is responsible for the voltage-resistant inhibition of alpha 1A (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 alpha 1 subunits with G beta gamma, whereas the latter has not been well characterized. Here, we show that the N-terminus of G alpha o is critical for the interaction with the C-terminus of the P/Q-type channel subunit, and that the binding induces voltage-resistant inhibition. A P/Q-type C-terminal peptide, an antiserum raised against the G alpha o N-terminus, and a G alpha o N-terminal peptide all attenuated the voltage-resistant inhibition of P/Q-type 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 P/Q-type channel C-terminal or G alpha o N-terminal peptide. Although the C-terminal domain of the N-type channel showed similar ability to binding with G alpha o N-terminus, the above-mentioned treatments were ineffective in the N-type channel current. These findings demonstrate that the voltage-resistant inhibition of the P/Q-type channel is caused by the interaction between the C-terminal domain of the Ca2+ channel alpha 1A subunit and the N-terminal region of G alpha o.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. marix@marine.email.ne.jp
Mariko
M
Kinoshita
D000818:Animals; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000378:metabolism*; D017097:Electric Impedance; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding
D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020962:Heterotrimeric GTP-Binding Proteins