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J. Biol. Chem., Vol. 276, Issue 31, 28731-28738, August 3, 2001

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Binding of G_o N Terminus Is Responsible for the Voltage-resistant Inhibition of _1A (P/Q-type, Ca_v2.1) Ca²⁺ Channels^*

Mariko Kinoshita, Toshihide Nukada^§, Tomiko Asano^¶, Yasuo Mori, Akinori Akaike^**, Masamichi Satoh, and Shuji Kaneko^§§

From the Departments of  Neuropharmacology, ^** Pharmacology,  Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan, the ^§ Department of Neurochemistry, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan, the ^¶ Department of Biochemistry, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kagiya-cho, Kasugai 480-0392, Japan, and the  Center for Integrative Bioscience and Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki National Research Institutes, Okazaki 444-8585, Japan

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 ₁ subunits with G, whereas the latter has not been characterized well. Here, we show that the N terminus of G_o is critical for the interaction with the C terminus of the _1A channel subunit, and that the binding induces the voltage-resistant inhibition. An _1A C-terminal peptide, an antiserum raised against G_o N terminus, and a G_o N-terminal peptide all attenuated the voltage-resistant inhibition of _1A currents. Furthermore, the N terminus of G_o bound to the C terminus of _1A in vitro, which was prevented either by the _1A channel C-terminal or G_o N-terminal peptide. Although the C-terminal domain of the _1B channel showed similar ability in the binding with G_o N terminus, the above mentioned treatments were ineffective in the _1B channel current. These findings demonstrate that the voltage-resistant inhibition of the P/Q-type, _1A channel is caused by the interaction between the C-terminal domain of Ca²⁺ channel _1A subunit and the N-terminal region of G_o.

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