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

Date

2009-07-03

Authors

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

Journal Title

Journal ISSN

Volume Title

Publisher

EMBO Reports

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 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.

Description

Keywords

ion channel, G proteins, M3 muscarinic receptor, NALCN, Src

Citation

Swayne, 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.