Density of ryanodine receptors is increased in sarcoplasmic reticulum from prehypertrophic cardiomyopathic hamster heart.
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 (Bmax) and affinity (Kd) of [3H]-ryanodine binding sites in heavy SR fractions from 40-65 day-old normal and CM hamster hearts. Results showed that the Bmax was significantly increased in CM heart when compared to normal (Bmax = 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 Kd were similar in both groups. Sensitivity of [3H]-ryanodine binding to Ca2+ was unchanged, but the density of binding was increased at all Ca2+ concentrations which potentiated binding in CM heart. Similarly, potentiation of [3H]ryanodine binding by ATP and inhibition of binding by Mg2+ were intact in membranes from CM heart. Results demonstrate that the density [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 Ca2+ release from SR may contribute to the development of Ca2+ overload in this model of cardiomyopathy.
Sapp
J L
JL
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Howlett
S E
SE
D000367:Age Factors; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D008297:Male; D008647:Mesocricetus / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D012433:Ryanodine / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D015854:Up-Regulation
D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine