RT Journal Article SR Electronic T1 The α Subunit of Gq Contributes to Muscarinic Inhibition of the M-Type Potassium Current in Sympathetic Neurons JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4521 OP 4531 DO 10.1523/JNEUROSCI.18-12-04521.1998 VO 18 IS 12 A1 Jane E. Haley A1 Fe C. Abogadie A1 Patrick Delmas A1 Mariza Dayrell A1 Yvonne Vallis A1 Graeme Milligan A1 Malcolm P. Caulfield A1 David A. Brown A1 Noel J. Buckley YR 1998 UL http://www.jneurosci.org/content/18/12/4521.abstract AB Rat superior cervical ganglion (SCG) neurons express low-threshold noninactivating M-type potassium channels (IK(M)), which can be inhibited by activation of M1 muscarinic receptors. This inhibition occurs via pertussis toxin-insensitive G-proteins belonging to the Gαq 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 IK(M). These antisense plasmids specifically reduced levels of the target G-protein 48 hr after intranuclear injection. In cells depleted of Gαq, muscarinic inhibition of IK(M) was attenuated compared both with uninjected neurons and with neurons injected with an inappropriate GαoAantisense plasmid. In contrast, depletion of Gα11 protein did not alter IK(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 IK(M) at a concentration of plasmid that can reduce βγ-mediated inhibition of calcium current (Delmas et al., 1998a). Also, expression of β1γ2 dimers did not alter the IK(M) density in SCG neurons. In contrast, IK(M) was virtually abolished in cells expressing GTPase-deficient, constitutively active forms of Gαq and Gα11. These data suggest that Gαq is the principal mediator of muscarinic IK(M) inhibition in rat SCG neurons and that this more likely results from an effect of the α subunit than the βγ subunits of the Gqheterotrimer.