Binding of Gαo N-terminus is responsible for the voltage-resistant inhibition of α1A (P/Q-Type, Ca v2.1) Ca2+ channels

Abstract

G-protein-mediated inhibition of presynaptic voltage-dependent Ca 2+ channels is comprised of voltage-dependent and -resistant components. The former is caused by a direct interaction of Ca2+ channel α1 subunits with Gβγ, whereas the latter has not been well characterized. Here, we show that the N-terminus of Gαo 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 Gαo N-terminus, and a Gαo N-terminal peptide all attenuated the voltage-resistant inhibition of P/Q-type currents. Furthermore, the N-terminus of Gαo bound to the C-terminus of α1A in vitro, which was prevented either by the P/Q-type channel C-terminal or Gαo N-terminal peptide. Although the C-terminal domain of the N-type channel showed similar ability to binding with Gαo 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 α1A subunit and the N-terminal region of Gαo. © 2002 The Pharmaceutical Society of Japan.