Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice

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Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice.

In human cardiomyopathy, anatomical abnormalities such as hypertrophy and fibrosis contribute to the risk of ventricular arrhythmias and sudden death. Here we have shown that increased myofilament Ca2+ sensitivity, also a common feature in both inherited and acquired human cardiomyopathies, created arrhythmia susceptibility in mice, even in the absence of anatomical abnormalities. In mice expre...

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Myofilament Ca sensitization increases cytosolic Ca binding affinity, alters intracellular Ca homeostasis, and causes pause-dependent Ca-triggered arrhythmia.

RATIONALE Ca binding to the troponin complex represents a major portion of cytosolic Ca buffering. Troponin mutations that increase myofilament Ca sensitivity are associated with familial hypertrophic cardiomyopathy and confer a high risk for sudden death. In mice, Ca sensitization causes ventricular arrhythmias, but the underlying mechanisms remain unclear. OBJECTIVE To test the hypothesis t...

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Reversal of isoflurane-induced depression of myocardial contraction by nitroxyl via myofilament sensitization to Ca2+.

Isoflurane (ISO) is known to depress cardiac contraction. Here, we hypothesized that decreasing myofilament Ca(2+) responsiveness is central to ISO-induced reduction in cardiac force development. Moreover, we also tested whether the nitroxyl (HNO) donor 1-nitrosocyclohexyl acetate (NCA), acting as a myofilament Ca(2+) sensitizer, restores force in the presence of ISO. Trabeculae from the right ...

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8-bromo-cGMP reduces the myofilament response to Ca2+ in intact cardiac myocytes.

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2008

ISSN: 0021-9738

DOI: 10.1172/jci36642