Research ArticleCardiology

Sarcoplasmic reticulum calcium leak contributes to arrhythmia but not to heart failure progression

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Science Translational Medicine  12 Sep 2018:
Vol. 10, Issue 458, eaan0724
DOI: 10.1126/scitranslmed.aan0724

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Cardiac calcium clarified

The subcellular localization of calcium within cardiomyocytes is tightly regulated during the cardiac cycle, and calcium leak from the sarcoplasmic reticulum is linked to alterations in heart rhythm and heart failure. Mohamed et al. investigated whether inhibiting calcium leak by stabilizing the sarcoplasmic calcium channel ryanodine receptor 2 corrected irregular heartbeat and prevented maladaptive myocardial remodeling and heart failure. In a mouse model of pressure overload, reduced calcium leak did not prevent heart failure; increased calcium leak in a volume overload mouse model did not exacerbate heart failure. Rather, inhibiting calcium leak corrected arrhythmias in myocytes derived from patients with heart failure and tachycardia. Although myocardial remodeling was not altered, arrhythmia was mitigated and survival was increased by ryanodine receptor stabilization in mouse models, suggesting a potential therapeutic application for inhibiting sarcoplasmic calcium leak.