Abstract
Calcium overload has been linked to the development of cardiomyopathy in the cardiomyopathic (CM) hamster, but the site or sites of the lesion remain obscure. To determine whether the number of sarcoplasmic reticulum (SR) calcium release channels (ryanodine receptors) changes in the CM heart, we compared the density ( B max) and affinity ( K d) of [ 3H]-ryanodine binding sites in heavy SR fractions from 40-65 day-old normal and CM hamster hearts. Results showed that the B max was significantly increased in CM heart when compared to normal ( B max = 2489 ± 159 fmol/mg protein in normal heart and 3360 ±223 fmol/mg protein in CM heart, mean ± S.E., P = 0.01). [ 3H]-Ryanodine bound to a single, high affinity site in SR from both normal and CM hearts; values for K d were similar in both groups. Sensitivity of [ 3H]-ryanodine binding to Ca 2+ was unchanged, but the density of binding was increased at all Ca 2+ concentrations which potentiated binding in CM heart. Similarly, potentiation of [ 3H]-ryanodine binding by ATP and inhibition of binding by Mg 2+ were intact in membranes from CM heart. Results demonstrate that the density of [ 3H]-ryanodine receptors is increased in SR from CM hearts early in the development of cardiomyopathy, although the properties of these receptors are unchanged. This suggests an increase in the amount or velocity of Ca 2+ release from SR may contribute to the development of Ca 2+ overload in this model of cardiomyopathy.
Published Version
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