Alteration of Ca2+ release channel function in sarcoplasmic reticulum of pressure-overload-induced hypertrophic rat heart.
The effects of pressure-overload left ventricular hypertrophy on the Ca2+ release channel in sarcoplasmic reticulum (SR) were studied by [3H]ryanodine binding and 45Ca2+ flux measurements. The density of Ca2+ release channel in left ventricle determined by equilibrium [3H]ryanodine binding to whole homogenates was significantly lower in hypertrophy than sham (Bmax: 0.47 +/- 0.04 v 0.72 +/- 0.10 pmol/mg protein), whereas total number of Ca2+ release channels in whole left ventricle was similar in the two groups. Ryanodine binding to SR vesicles isolated by differential centrifugation was also similar in the two groups, but the SR yield was less in the hypertrophied left ventricle. The Ca2+ release channels in hypertrophied left ventricles showed a significantly increased sensitivity to Ca2+ release agonists (e.g. caffeine and doxorubicin), as characterized by the effects of these agonists on ryanodine binding to whole homogenates and Ca2+ release from isolated SR. These results indicate that pressure-overload left ventricular hypertrophy is associated with both qualitative and quantitative changes in Ca2+ release channel function.
Kim
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Department of Medicine, University of Connecticut Health Center, Farmington 06030-1305.
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Kim
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Caroll
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D009124:Muscle Proteins / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D004317:Doxorubicin; D002118:Calcium