The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic β-cell line
Version of Record online: 3 JUL 2009
Copyright © 2009 European Molecular Biology Organization
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 10, Issue 8, pages 873–880, August 2009
How to Cite
Swayne, L. A., Mezghrani, A., Varrault, A., Chemin, J., Bertrand, G., Dalle, S., Bourinet, E., Lory, P., Miller, R. J., Nargeot, J. and Monteil, A. (2009), The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic β-cell line. EMBO reports, 10: 873–880. doi: 10.1038/embor.2009.125
- Issue online: 1 AUG 2009
- Version of Record online: 3 JUL 2009
- Manuscript Accepted: 29 APR 2009
- Manuscript Revised: 27 APR 2009
- Manuscript Received: 9 DEC 2008
- ion channel;
- G proteins;
- M3 muscarinic receptor;
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.