Reduced activity in the sodium channels of the heart could be responsible for a variety of arrhythmias, a murine study in the Proceedings of the National Academy of Sciences suggests.
Genetic mutations relating to the cardiac sodium channel have been associated with a wide range of arrhythmias in patients, including bradycardia, atrioventricular conduction delay, and ventricular fibrillation. However, the pathophysiological basis of these conditions remains unresolved.
To investigate further, G Alex Papadatos, from the University of Cambridge, UK, and colleagues examined the effects of a null mutation in the mouse sodium channel gene, Scn5a.
The team found that mice homozygous for the defective gene died in utero, with severe defects in ventricular morphogenesis, whereas those with only one copy of the defective gene showed normal survival.
However, analysis of isolated ventricular myocytes from adult heterozygous Scn5a+/- mice demonstrated a 50% reduction in sodium conductance.
The team observed that the Scn5a+/- hearts had several defects, including impaired atrioventricular conduction, delayed intramyocardial conduction, increased ventricular refractoriness, and ventricular tachycardia, with characteristics of reentrant excitation.
The findings provide a possible link between reduced cardiac sodium channel activity and apparently adverse clinical phenotypes, they say.
Papadatos et al conclude: 'These results, taken together with those obtained from computer modeling and clinical observations, suggest that slow conduction as a result of sodium channel dysfunction represents a critical target for understanding and managing cardiac arrhythmias.'