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

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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.