Ca2+ channel beta3 subunit enhances voltage-dependent relief of G-protein inhibition induced by muscarinic receptor activation and Gbetagamma.
The Ca2+ channel beta 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 beta3 subunit causes M2 muscarinic receptor-mediated inhibition of alpha1B Ca2+ currents to become more voltage-dependent. We report here that the beta3 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 alpha1B channels to G-protein-mediated inhibition seen after coexpression of the Ca2+ channel beta3 subunit. Additionally, the beta3 subunit alters the rate and voltage dependency of relief of the inhibition produced by coexpressed Gbeta1gamma1, in a manner similar to the changes it produces in relief of M2 receptor-induced inhibition. We conclude that the Ca2+ channel beta3 subunit reduces the magnitude of G-protein inhibition of alpha1B Ca2+ channels by enhancing the rate of dissociation of the G-protein betagamma subunit from the Ca2+ channel alpha1B subunit.
Roche
J P
JP
Department of Pharmacology and Molecular Toxicology and Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Treistman
S N
SN
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014981:Xenopus
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D005033:Ethylmaleimide