Binding of G alpha(o) N terminus is responsible for the voltage-resistant inhibition of alpha(1A) (P/Q-type, Ca(v)2.1) Ca(2+) channels.
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 Ca(2+) channel alpha(1) 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 Ca(2+) channel alpha(1A) subunit and the N-terminal region of G alpha(o).
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Brain, Calcium Channel Blockers, Calcium Channels, N-Type, Cattle, Female, GTP-Binding Protein alpha Subunits, Gi-Go, Heterotrimeric GTP-Binding Proteins, Kinetics, Membrane Potentials, Molecular Sequence Data, Oocytes, Ovary, Peptide Fragments, Peptides, Protein Subunits, Recombinant Fusion Proteins, Recombinant Proteins, Xenopus laevis
Amino Acid Sequence, Animals, Binding Sites, Brain, Calcium Channel Blockers, Calcium Channels, N-Type, Cattle, Female, GTP-Binding Protein alpha Subunits, Gi-Go, Heterotrimeric GTP-Binding Proteins, Kinetics, Membrane Potentials, Molecular Sequence Data, Oocytes, Ovary, Peptide Fragments, Peptides, Protein Subunits, Recombinant Fusion Proteins, Recombinant Proteins, Xenopus laevis
J. Biol. Chem.
Date: Aug. 03, 2001
PubMed ID: 11395521
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