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  • Title: Role of ryanodine receptor as a Ca²(+) regulatory center in normal and failing hearts.
    Author: Yano M, Yamamoto T, Kobayashi S, Matsuzaki M.
    Journal: J Cardiol; 2009 Feb; 53(1):1-7. PubMed ID: 19167631.
    Abstract:
    Abnormal Ca²(+) cycling is important in various cardiac diseases. Evidence has accumulated that dysregulation of Ca²(+) release from the ryanodine receptor (RyR2) plays a significant role in cardiac dysfunction. Spontaneous Ca²(+) release through RyR2 during diastole decreases sarcoplasmic reticulum (SR) Ca²(+) content, and also induces delayed after depolarization (DAD) as a substrate for lethal arrhythmia. Several disease-linked mutations in the RyR have been reported in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) or arrythmogenic right ventricular cardiomyopathy type 2 (ARVC2). The unique distribution of these mutation sites has produced the concept that the interaction among the putative regulatory domains within the RyR may play a key role in regulating the channel opening, and that there seems to be a common abnormality in the channel disorder between heart failure and CPVT/ARVC2. We review here the considerable body of evidence regarding defective channel gating of RyR2 in the pathogenesis of heart failure and lethal arrhythmia.
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