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.