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

Leigh Anne Swayne, Alexandre Mezghrani, Annie Varrault, Jean Chemin, Gyslaine Bertrand, Stephane Dalle, Emmanuel Bourinet, Philippe Lory, Richard J. Miller, Joel Nargeot, Arnaud Monteil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)873-880
Number of pages8
JournalEMBO Reports
Volume10
Issue number8
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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