Analysis of a unique cation channel (LNALCN) that can either be a calcium channel or a sodium channel

分析独特的阳离子通道 (LNALCN)，可以是钙通道或钠通道

• 批准号: 328289-2011
• 负责人: Spafford, David
• 金额: $ 2.62万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572145
• 关键词: Analysis; unique; cation; channel; LNALCN

The excitability of a cell depends on the regulation of ion flow through ion channels, such as cation channels that pass sodium ions or calcium ions. The two worlds that sodium and calcium ions service in ion channels are different. Sodium is an inert charge carrier, that serves to excite cell membranes such as in nerve action potentials. Calcium ions increase transiently inside cells to trigger signaling in cells. While cells tolerate high sodium ion concentrations, resting concentrations of calcium is at least 50,000 times lower than sodium ions. The exclusivity of the calcium signal through calcium channels is a symmetrical filter in the ion channel pore that provides 10,000 fold selectivity of calcium ions over sodium ions. Sodium channels possess an asymmetrical pore filter that is less discriminatory against rival cations. We have found that alternative versions of the snail NALCN channel replaces the asymmetrical pore with a symmetrical pore that looks like a calcium channel pore. We report that the snail NALCN form LNALCN-Ca has a symmetrical pore that is highly selective for calcium ions and a second form, LNALCN-Na has an asymmetrical pore that is highly selective for sodium ions. Only the snail NALCN out of all reported genomes, contains two forms of a pore-forming exon, which engenders NALCN with a unique capacity to permeate either calcium ions (LNALCN-Ca) or mostly sodium ions (LNALCN-Na). NALCN is a highly novel channel, first reported as a leak sodium conductance channel in the Journal, Cell (2007) and in a follow up paper appeared in Nature in 2009. We redefine this novel leak sodium conductance channel as a potential calcium channel. Our report of an ion channel that can switch its ion selectivity through alternative splicing is one of the most novel findings in ion channel research, and its analyses forms the basis of this NSERC Discovery Grant.

细胞的兴奋性取决于离子通道的离子流的调节，例如通过钠离子或钙离子的阳离子通道。 离子通道中钠和钙离子服务的两个世界不同。 钠是一种惰性电荷载体，可激发细胞膜（例如神经作用电位）。钙离子在细胞内部瞬时增加，以触发细胞中的信号传导。 虽然细胞耐受高钠离子浓度，但静脉浓度的钙比钠离子低50,000倍。 钙信号通过钙通道的排他性是离子通道孔中的对称过滤器，在钠离子上提供了10,000倍的钙离子的选择性。 钠通道具有不对称的孔滤波器，对竞争阳离子的歧视性较小。 我们发现，蜗牛NALCN通道的替代版本用看起来像钙通道孔的对称孔代替了不对称的孔。我们报告说，蜗牛NALCN形式的Lnalcn-Ca具有对称孔，对钙离子具有高度选择性，而第二种形式的Lnalcn-Na具有不对称的孔，对钠离子具有高度选择性。 只有所有报道的基因组中的蜗牛nalcn包含两种形式的孔形外显子，它们具有独特的能力，可以渗透到钙离子（Lnalcn-Ca）或主要是钠离子（Lnalcn-NA）。 NALCN是一个高度新颖的通道，首先据报道是《杂志》（Cell（2007））中的泄漏钠电导通道，在2009年在自然界中出现的后续文件中。我们重新定义了这种新颖的泄漏钠电导通道作为潜在的钙通道。 我们关于可以通过替代剪接切换其离子选择性的离子渠道的报告是离子通道研究中最新颖的发现之一，其分析构成了该NSERC Discovery Grant的基础。