Role of ryanodine receptor as a Ca²(+) regulatory center in normal and failing hearts.
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.
Yano
Masafumi
M
Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. yanoma@yamaguchi-u.ac.jp
Yamamoto
Takeshi
T
Kobayashi
Shigeki
S
Matsuzaki
Masunori
M
D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium