Key result
Defective interdomain interaction within the ryanodine receptor, leading to domain unzipping and Ca2+ leak, appears to be a critical initial step in the pathogenesis of heart failure.
Why the study?
Does defective interdomain interaction within the ryanodine receptor cause Ca2+ leak and contribute to the pathogenesis of heart failure?
Population
Dog left ventricular muscles and isolated myocytes, including pacing-induced dog failing hearts
Comparison
Addition of DPc10 vs Baseline/normal state without DPc10, and normal…
Design
Preclinical
Authors
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Suggests ryanodine receptor stabilizers merit preclinical testing in heart failure; leaves open clinical translation.
Does defective interdomain interaction within the ryanodine receptor cause Ca2+ leak and contribute to the pathogenesis of heart failure?
Defective interdomain interaction within the ryanodine receptor leads to Ca2+ leak and appears to be a critical initial step in the pathogenesis of heart failure.
Oda et al. (2005) studied Heart failure. DPc10 synthetic peptide was evaluated on Domain unzipping, Ca2+ leak, and FKBP12.6 dissociation. Defective interdomain interaction within the ryanodine receptor, leading to domain unzipping and Ca2+ leak, appears to be a critical initial step in the pathogenesis of heart failure.
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