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Normalizing calcium flux to treat atrial fibrillation

May. 12, 2014, 2:00 PM

Illustration of heart
(iStock)

Atrial fibrillation (AF) – the most common disorder of heart rhythm – has multiple causes, including inherited mutations in proteins that regulate calcium levels (RyR2 channels and calsequestrin).

Björn Knollmann, M.D., Ph.D., and colleagues used a mouse model to examine how loss of calsequestrin causes AF. In the atria of mice missing calsequestrin, the investigators observed spontaneous calcium elevations and delayed afterdepolarizations (DADs) – electrical changes that can trigger abnormal heart rhythms. They demonstrated that the anti-arrhythmic drug R-propafenone, which inhibits both RyR2 and sodium channels, reduced the frequency and amplitude of calcium elevations and DADs, and prevented induction of AF. Drugs that inhibited only sodium, but not RyR2, channels did not prevent AF.

The findings, reported in the April issue of Circulation: Arrhythmia and Electrophysiology, support the hypothesis that loss of calsequestrin increases risk of AF by promoting spontaneous calcium elevations and DADs. R-propafenone prevents calcium elevation and electrical triggers of AF and offers a mechanism-based approach for treating this common arrhythmia.

This research was supported in part by National Institutes of Health grants HL088635, HL071670, HL108173, HL092217, by an Australian National Health and Medical Research Council Project Grant and by an AHA Innovative Research Grant.

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