Leaky transmembrane channels could cause disruptions in normal heart function, reveal researchers in Canada. Unusual cardiac arrhythmias can occur due to ion leaks in mutant sodium channels, suggests the study.
Voltage-gated sodium (Nav) channels are responsible for mediating an "action potential" in muscle cells that leads to contraction. Nav1.5 is the primary Nav channel expressed in the muscle cells of the heart, and Nav1.5 mutations that disrupt its function are associated with many well-defined cardiac arrhythmias. Recent studies have linked two Nav1.5 mutations (R222Q and R225W) to an unusual group of arrhythmias that are associated with dilated cardiomyopathy, a condition in which the heart becomes enlarged and cannot pump blood efficiently.
Oddly enough, the two mutant channels have opposite effects on channel function, with one expected to promote premature firing of the action potential and the other expected to interfere with action potential initiation. It's therefore unclear how they could be linked to similar cardiac pathologies.
Chahine and colleagues think that the resulting overload of sodium ions within the cell could contribute to disruptions in normal cardiac function. And because the ion leak is the only property common to both mutations, their findings suggest that it could be a key mechanism linking them-and possibly other Nav1.5 mutations in the VSD-to the atypical group of arrhythmias mixed with dilated cardiomyopathy.
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Research reported in the press release was supported by The Heart and Stroke Foundation of Quebec, the Canadian Institutes of Health Research, and the National Science Foundation.