title: The NALCN ion channel is a new actor in pancreatic β-cell physiology.
abstract: Ion channels are critical components of cell excitability involved in many physiological processes, including hormone secretion, and are thought be targets of choice in a pathological context. In the present paper, we summarize and discuss our recent findings on a four domain cation channel named NALCN which has been previously described as mediating a TTX-resistant leak sodium current in neurons. We recently reported that NALCN is also expressed in rodent islets of Langerhans as well as in the mouse MIN6 pancreatic β-cell line. This pancreatic NALCN channel encodes for a cation current triggered by acetylcholine activation of M3 muscarinic receptors. Importantly, the activation mechanism is independent of G protein action, but is dependent on a SFK-pathway, and involves the co-inclusion of M3 muscarinic receptors and NALCN in the same complex. Although additional work is now needed, considering the importance of the cholinergic control on the pancreatic β-cell function, this study has unravelled the molecular identity of a new actor in pancreatic β-cell excitability that could be a major target for new compounds modulating insulin secretion.
authors.affiliation: Institut de Génomique Fonctionnelle, CNRS, UMR, INSERM U, Universités Montpellier I&II, France.
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Swayne
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mezghrani
authors.forename: Philippe
authors.initials: P
authors.lastname: Lory
authors.forename: Joel
authors.initials: J
authors.lastname: Nargeot
authors.forename: Arnaud
authors.initials: A
authors.lastname: Monteil
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D012377:Rodentia
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; C519922:NALCN protein, mouse; D009419:Nerve Tissue Proteins