title: The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic beta-cell line.
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 beta-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.
authors: Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Montpellier, France.
authors: Leigh Anne
authors: LA
authors: Swayne
authors: Alexandre
authors: A
authors: Mezghrani
authors: Annie
authors: A
authors: Varrault
authors: Jean
authors: J
authors: Chemin
authors: Gyslaine
authors: G
authors: Bertrand
authors: Stephane
authors: S
authors: Dalle
authors: Emmanuel
authors: E
authors: Bourinet
authors: Philippe
authors: P
authors: Lory
authors: Richard J
authors: RJ
authors: Miller
authors: Joel
authors: J
authors: Nargeot
authors: Arnaud
authors: A
authors: Monteil
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D004791:Enzyme Inhibitors; D007473:Ion Channels; D011720:Pyrazoles; D011743:Pyrimidines; D034741:RNA, Small Interfering; D043587:Receptor, Muscarinic M3