Institut de Génomique Fonctionnelle, CNRS, UMR, INSERM U, Universités Montpellier I&II, France.
Islets. 2010 Jan-Feb;2(1):54-6. doi: 10.4161/isl.2.1.10522.
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.
离子通道是参与许多生理过程的细胞兴奋性的关键组成部分，包括激素分泌，并且被认为是病理情况下的首选靶点。在本文中，我们总结并讨论了我们最近关于一种名为 NALCN 的四结构域阳离子通道的发现，该通道先前被描述为介导神经元中的 TTX 抗性渗漏钠电流。我们最近报道 NALCN 也在啮齿动物胰岛以及小鼠 MIN6 胰腺β细胞系中表达。这种胰腺 NALCN 通道编码一种由乙酰胆碱激活 M3 毒蕈碱受体引发的阳离子电流。重要的是，激活机制不依赖于 G 蛋白作用，而是依赖于 SFK 途径，并且涉及 M3 毒蕈碱受体和 NALCN 包含在同一复合物中。尽管现在需要更多的工作，但考虑到胆碱能对胰腺β细胞功能的控制的重要性，这项研究揭示了胰腺β细胞兴奋性的新分子身份，这可能是调节胰岛素分泌的新化合物的主要靶标。
