The α subunit of G(q) contributes to muscarinic inhibition of the M- type potassium current in sympathetic neurons

J.E. Haley, F.C. Abogadie, P. Delmas, M. Dayrell, Y. Vallis, D.A. Brown, N.J. Buckley, M.P. Caulfield, G. Milligan

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Rat superior cervical ganglion (SCG) neurons express low-threshold noninactivating M-type potassium channels (I(K(M))), which can be inhibited by activation of M1 muscarinic receptors. This inhibition occurs via pertussis toxin-insensitive G-proteins belonging to the Gα(q) family (Caulfield et al., 1994). We have used DNA plasmids encoding antisense sequences against the 3' untranslated regions of Gα subunits (antisense plasmids) to investigate the specific G-protein subunits involved in muscarinic inhibition of I(K(M)). These antisense plasmids specifically reduced levels of the target G-protein 48 hr after intranuclear injection. In cells depleted of Gα(q), muscarinic inhibition of I(K(M)) was attenuated compared both with uninjected neurons and with neurons injected with an inappropriate Gα(oA) antisense plasmid. In contrast, depletion of Gα protein did not alter I(K(M)) inhibition. To determine whether the α or βγ subunits of the G-protein mediated this inhibition, we have overexpressed the C terminus of β adrenergic receptor kinase 1 (βARK1), which binds free βγ subunits. βARK1 did not reduce muscarinic inhibition of I(K(M)) at a concentration of plasmid that can reduce βγ-mediated inhibition of calcium current (Delmas et al., 1998a). Also, expression of β(1γ2) dimers did not alter the I(K(M)) density in SCG neurons. In contrast, I(K(M)) was virtually abolished in cells expressing GTPase-deficient, constitutively active forms of Gα(q) and Gα. These data suggest that Gα(q) is the principal mediator of muscarinic I(K(M)) inhibition in rat SCG neurons and that this more likely results from an effect of the subunit than the βγ subunits of the G(q) heterotrimer.
Original languageEnglish
Pages (from-to)4521-4531
Number of pages11
JournalJournal of Neuroscience
Issue number12
Publication statusPublished - 15 Jun 1998


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