Exendin-4 Reduces Ventricular Arrhythmia Activity and Calcium Sparks-Mediated Sarcoplasmic Reticulum Ca Leak in Rats with Heart Failure

, which was longer in the heart failure model, and increase the APD alternans thresholds. Exendin-4 also reduced the susceptibility to burst pacing-induced arrhythmia ex vivo. Subcellular sarcoplasmic reticulum (SR) calcium leak characteristics were tested in four groups of rat cardiomyocytes. Exendin-4 reduced calcium spark mass, spark frequency, and calcium leak, which may be due to reduced S2814-RyR2 and CaMK-II phosphorylation. Co-administration of exendin 9-39 with exendin-4 partly abolished the above-mentioned effect of exendin-4.These findings suggest that exendin-4 exerts an antiarrhythmic effect through decreasing SR calcium leak in spontaneous and burst pacing-induced ventricular arrhythmias, which may be due to reduced RyR2 phosphorylation and suppressed CaMK-II activity. Exendin-4 may act as a novel antiarrhythmic strategy in heart failure.