The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic ß-cell line

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dc.contributor.authorSwayne, Leigh Anne
dc.contributor.authorMezghrani, Alexandre
dc.contributor.authorVarrault, Annie
dc.contributor.authorChemin, Jean
dc.contributor.authorBertrand, Gyslaine
dc.contributor.authorDalle, Stephane
dc.contributor.authorBourinet, Emmanuel
dc.contributor.authorLory, Philippe
dc.contributor.authorMiller, Richard J.
dc.contributor.authorNargeot, Joel
dc.contributor.authorMonteil, Arnaud
dc.date.accessioned2016-03-11T14:07:22Z
dc.date.available2016-03-11T14:07:22Z
dc.date.copyright2009en_US
dc.date.issued2009-07-03
dc.description.abstractA previously uncharacterized putative ion channel, NALCN (sodium leak channel, non-selective), has been recently shown to be responsible for the tetrodotoxin (TTX)-resistant sodium leak current implicated in the regulation of neuronal excitability. Here, we show that NALCN encodes a current that is activated by M3 muscarinic receptors (M3R) in a pancreatic b-cell line. This current is primarily permeant to sodium ions, independent of intracellular calcium stores and G proteins but dependent on Src activation, and resistant to TTX. The current is recapitulated by co-expression of NALCN and M3R in human embryonic kidney-293 cells and in Xenopus oocytes. We also show that NALCN and M3R belong to the same protein complex, involving the intracellular I–II loop of NALCN and the intracellular i3 loop of M3R. Taken together, our data show the molecular basis of a muscarinic-activated inward sodium current that is independent of G-protein activation, and provide new insights into the properties of NALCN channels.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipWe thank E. Lutz, M. Hosey and D. Trono for kindly providing some of the constructs used in this study, C. Barre`re and I. Bidaud for technical assistance, and T.P. Snutch and J. Bockaert for comments on the paper. L.A.S. was supported by a Marie Curie Incoming International Postdoctoral Fellowship. This work was supported by the Programme National de Recherche sur le Diabéte de l’Institut National de la Santé et de la Recherche Médicale, as well as by the Association de Recherche sur le Diabéte.en_US
dc.identifier.citationSwayne, L.A., Mezghrani, A., Varrault, A., Chemin, J., Bertrand, G., Dalle, S., ... Monteil, A. (2009). The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic ß-cell line. EMBO Reports, 10(8), 873-880.en_US
dc.identifier.urihttp://dx.doi.org/10.1038/embor.2009.125
dc.identifier.urihttp://hdl.handle.net/1828/7073
dc.language.isoenen_US
dc.publisherEMBO Reportsen_US
dc.rightsAttribution-NonCommercial-NoDerivs 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/ca/*
dc.subjection channel
dc.subjectG proteins
dc.subjectM3 muscarinic receptor
dc.subjectNALCN
dc.subjectSrc
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.titleThe NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic ß-cell lineen_US
dc.typeArticleen_US

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