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 G
1
1,
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
Copyright © 1998 Society for Neuroscience 0270-6474/98/18134883-08$05.00/0
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