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

Haley, Jane E. and Delmas, Patrick and Offermanns, Stefan and Abogadie, Fe C. and Simon, Melvin I. and Buckley, Noel J. and Brown, David A. (2000) Muscarinic Inhibition of Calcium Current and M Current in Gα_q-Deficient Mice. Journal of Neuroscience, 20 (11). pp. 3973-3979. ISSN 0270-6474. PMCID PMC6772644. https://resolver.caltech.edu/CaltechAUTHORS:20191028-091347044

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1523/jneurosci.20-11-03973.2000DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772644PubMed CentralArticle
ORCID:
AuthorORCID
Brown, David A.0000-0002-9180-5765
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.
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
Medical Research Council (UK)UNSPECIFIED
Subject Keywords:M current; calcium current; G-protein; superior cervical ganglion neuron; knock-out mouse; muscarinic receptor; bradykinin receptor
Issue or Number:11
PubMed Central ID:PMC6772644
Record Number:CaltechAUTHORS:20191028-091347044
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191028-091347044
Official Citation:Muscarinic Inhibition of Calcium Current and M Current in Gαq-Deficient Mice. Jane E. Haley, Patrick Delmas, Stefan Offermanns, Fe C. Abogadie, Melvin I. Simon, Noel J. Buckley, David A. Brown. Journal of Neuroscience 1 June 2000, 20 (11) 3973-3979; DOI: 10.1523/JNEUROSCI.20-11-03973.2000
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99482
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:28 Oct 2019 17:11
Last Modified:09 Mar 2020 13:18

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