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The Journal of Neuroscience, July 1, 1998, 18(13):4883-4890

Ca²⁺ Channel ₃ Subunit Enhances Voltage-Dependent Relief of G-Protein Inhibition Induced by Muscarinic Receptor Activation and G

John P. Roche and Steven N. Treistman

Department of Pharmacology and Molecular Toxicology and Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts 01655

The Ca²⁺ channel  subunit has been shown to reduce the magnitude of G-protein inhibition of Ca²⁺ channels. However, neither the specificity of this action to different forms of G-protein inhibition nor the mechanism underlying this reduction in response is known. We have reported previously that coexpression of the Ca²⁺ channel ₃ subunit causes M₂ muscarinic receptor-mediated inhibition of _1B Ca²⁺ currents to become more voltage-dependent. We report here that the ₃ subunit increases the rate of relief of inhibition produced by a depolarizing prepulse and also shifts the voltage dependency of this relief to more hyperpolarized voltages; these effects are likely to be responsible for the reduction of inhibitory response of _1B channels to G-protein-mediated inhibition seen after coexpression of the Ca²⁺ channel ₃ subunit. Additionally, the ₃ subunit alters the rate and voltage dependency of relief of the inhibition produced by coexpressed G₁₁, in a manner similar to the changes it produces in relief of M₂ receptor-induced inhibition. We conclude that the Ca²⁺ channel ₃ subunit reduces the magnitude of G-protein inhibition of _1B Ca²⁺ channels by enhancing the rate of dissociation of the G-protein subunit from the Ca²⁺ channel _1B subunit.

Key words: Ca²⁺ channels; G-proteins; _1A; _1B; Ca²⁺ channel  subunit; G-protein  subunit; G-protein subunit; voltage-dependent inhibition; Xenopus oocyte; muscarinic M₂ receptor; NEM

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18134883-08$05.00/0

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