Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published June 1, 2000 | Published
Journal Article Open

Muscarinic Inhibition of Calcium Current and M Current in Gα_q-Deficient Mice


Activation of M₁ muscarinic acetylcholine receptors (M₁ 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 M₁ 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, M₁mAChR 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 IK(M) in rat SCG neurons via a PTX-insensitive G-protein (G_q and/or G₁₁; 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) M₁ mAChR inhibition of I_(Ca) is mediated principally by G_q, (2) M₁ mAChR inhibition of I_(K(M)) is mediated partly by G_q, more substantially by G₁₁, and partly by a PTX-sensitive G-protein(s), and (3) BK-induced inhibition of I_(K(M)) is mediated wholly by G₁₁.

Additional Information

© 2000 Society for Neuroscience. Received Nov. 9, 1999; revised Feb. 28, 2000; accepted March 17, 2000. This work was supported by the and the UK Medical Research Council. We thank Mariza Dayrell, Brenda Browning, and Misbah Malik-Hall for tissue culture expertise and Prof. Graeme Milligan (Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK) for the gift of Gao and Gaq/11 antisera.

Attached Files

Published - 3973.full.pdf


Files (257.2 kB)
Name Size Download all
257.2 kB Preview Download

Additional details

August 21, 2023
October 18, 2023