Key result
In failing canine hearts, defective inter-domain interaction within RyR2 reduced CaM binding affinity, causing spontaneous Ca2+ sparks that were attenuated by high concentrations of CaM.
Why the study?
Does defective calmodulin binding to RyR2 cause aberrant Ca2+ release in pacing-induced failing canine hearts?
Population
Normal and pacing-induced failing canine hearts and saponin-permeabilized cardiomyocytes
Comparison
Dantrolene, FK506, or high concentration of… vs Normal sarcoplasmic reticulum or untreated…
Design
Preclinical
Authors
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Reduced CaM-RyR2 binding may guide targeted HF therapies; leaves open clinical relevance pending human studies.
Does defective calmodulin binding to RyR2 cause aberrant Ca2+ release in pacing-induced failing canine hearts?
Defective inter-domain interaction within RyR2 reduces calmodulin binding affinity, leading to aberrant spontaneous Ca2+ release in heart failure, which can be corrected by dantrolene or exogenous calmodulin.
Ono et al. (2010) studied Heart failure. Dantrolene and Calmodulin vs. Untreated failing sarcoplasmic reticulum or cardiomyocytes was evaluated on CaM-binding affinity to RyR2 and frequency of spontaneous Ca2+ sparks. In failing canine hearts, defective inter-domain interaction within RyR2 reduced CaM binding affinity, causing spontaneous Ca2+ sparks that were attenuated by high concentrations of CaM.
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