The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic β-cell line |
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| Authors: | Leigh Anne Swayne Alexandre Mezghrani Annie Varrault Jean Chemin Gyslaine Bertrand Stephane Dalle Emmanuel Bourinet Philippe Lory Richard J Miller Joel Nargeot Arnaud Monteil |
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| Affiliation: | 1. Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, 34094 Montpellier, France;2. Institut National de la Santé et de la Recherche Médicale, Unité 661, 34094 Montpellier, France;3. Universités Montpellier I & II, 141 Rue de la Cardonille, 34094 Montpellier, France;4. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, Illinois, 60611‐3008 USA |
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| Abstract: | A 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 β-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. |
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| Keywords: | ion channel G proteins M3 muscarinic receptor NALCN Src |
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