Publication Date:
2012-06-01
Description:
Brugada syndrome (BrS) is associated with ventricular tachycardia originating particularly in the right ventricle (RV). We explore electrophysiological features predisposing to such arrhythmic tendency and their possible RV localization in a heterozygotic Scn5a+/− murine model. Na v 1.5 mRNA and protein expression were lower in Scn5a+/− than wild-type (WT), with a further reduction in the RV compared with the left ventricle (LV). RVs showed higher expression levels of K v 4.2, K v 4.3 and KChIP2 in both Scn5a+/− and WT. Action potential upstroke velocity and maximum Na + current ( I Na ) density were correspondingly decreased in Scn5a+/− , with a further reduction in the RV. The voltage dependence of inactivation was shifted to more negative values in Scn5a+/−. These findings are predictive of a localized depolarization abnormality leading to slowed conduction. Persistent Na + current ( I pNa ) density was decreased in a similar pattern to I Na . RV transient outward current ( I to ) density was greater than LV in both WT and Scn5a+/− , and had larger time constants of inactivation. These findings were also consistent with the observation that AP durations were smallest in the RV of Scn5a+/− , fulfilling predictions of an increased heterogeneity of repolarization as an additional possible electrophysiological mechanism for arrhythmogenesis in BrS.
Electronic ISSN:
2046-2441
Topics:
Biology
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