TY - JOUR
T1 - The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic β-cell line
AU - Swayne, Leigh Anne
AU - Mezghrani, Alexandre
AU - Varrault, Annie
AU - Chemin, Jean
AU - Bertrand, Gyslaine
AU - Dalle, Stephane
AU - Bourinet, Emmanuel
AU - Lory, Philippe
AU - Miller, Richard J.
AU - Nargeot, Joel
AU - Monteil, Arnaud
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1038/embor.2009.125
DO - 10.1038/embor.2009.125
M3 - Article
C2 - 19575010
AN - SCOPUS:68249089016
SN - 1469-221X
VL - 10
SP - 873
EP - 880
JO - EMBO Reports
JF - EMBO Reports
IS - 8
ER -