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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Swayne LA,Mezghrani A,Varrault A,Chemin J,Bertrand G,Dalle S,Bourinet E,Lory P,Miller RJ,Nargeot J,Monteil A

doi

10.1038/embor.2009.125

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

873-80

issue

8

eissn

1469-221X

issn

1469-3178

pii

embor2009125

journal_volume

10

pub_type

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