Muscarinic inhibition of calcium current and M current in Gα(q)- deficient mice

J.E. Haley, P. Delmas, F.C. Abogadie, N.J. Buckley, D.A. Brown, S. Offermanns, M.I. Simon

Research output: Contribution to journalArticlepeer-review

Abstract

Activation of M muscarinic acetylcholine receptors (M mAChR) inhibits M-type potassium currents (I(K(M))) and N-type calcium currents (I(Ca)) in mammalian sympathetic ganglia. Previous antisense experiments suggested that, in rat superior cervical ganglion (SCG) neurons, both effects were partly mediated by the G-protein Gα(q) (Delmas et al., 1998a; Haley et al., 1998a), but did not eliminate a contribution by other pertussis toxin (PTX)-insensitive G-proteins. We have tested this further using mice deficient in the Gα(q) gene. PTX-insensitive M mAChR inhibition of I(Ca) was strongly reduced in Gα(q) -/- mouse SCG neurons and was fully restored by acute overexpression of Gα(q). In contrast, M mAChR inhibition of I(K(M)) persisted in Gα(q) -/- mouse SCG cells. However, unlike rat SCG neurons, muscarinic inhibition of I(K(M)) was partly PTX-sensitive. Residual (PTX-insensitive) I(K(M)) inhibition was slightly reduced in Gα(q) -/- neurons, and the remaining response was then suppressed by anti-Gα(q/11) antibodies. Bradykinin (BK) also inhibits I(K(M)) in rat SCG neurons via a PTX-insensitive G-protein (G(q) and/or G; Jones et al., 1995). In mouse SCG neurons, I(K(M)) inhibition by BK was fully PTX-resistant. It was unchanged in Gα(q) -/- mice but was abolished by anti-Gα(q/11) antibody. We conclude that, in mouse SCG neurons (1) M mAChR inhibition of I(Ca) is mediated principally by G(q), (2) M mAChR inhibition of I(K(M)) is mediated partly by G(q), more substantially by G, and partly by a PTX-sensitive G- protein(s), and (3) BK-induced inhibition of I(K(M)) is mediated wholly by G.
Original languageEnglish
Pages (from-to)3973-3979
Number of pages7
JournalJournal of Neuroscience
Volume20
Issue number11
Publication statusPublished - 1 Jun 2000

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