Mechanisms of ryanodine receptor 2 dysfunction in heart failure

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Mechanisms of diastolic dysfunction in heart failure.

Abnormalities of diastole are common to most forms of congestive heart failure (HF). Diastolic function is broadly defined as the ability of the heart to fill adequately and at normal pressure to charge the ventricular pump for each subsequent contraction. It is determined by both active and passive processes occurring at the level of the myocyte, extracellular matrix, and left ventricular cham...

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Ryanodine receptor dysfunction and triggered activity in the heart.

Arrhythmogenesis has been increasingly linked to cardiac ryanodine receptor (RyR) dysfunction. However, the mechanistic relationship between abnormal RyR function and arrhythmogenesis in the heart is not clear. We hypothesize that, under abnormal RyR conditions, triggered activity will be caused by spontaneous calcium release (SCR) events that depend on transmural heterogeneities of calcium han...

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Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca(2+) release in heart failure.

AIMS Calmodulin (CaM) is well known to modulate the channel function of the cardiac ryanodine receptor (RyR2). However, the possible role of CaM on the aberrant Ca(2+) release in diseased hearts remains unclear. In this study, we investigated the state of RyR2-bound CaM and channel dysfunctions in pacing-induced failing hearts. METHODS AND RESULTS The characteristics of CaM binding to RyR2 an...

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ژورنال

عنوان ژورنال: Nature Reviews Cardiology

سال: 2020

ISSN: 1759-5002,1759-5010

DOI: 10.1038/s41569-020-00443-x