CELLULAR FUNCTIONS OF DIABETIC CARDIOMYOCYTES - CONTRACTILITY, RAPID-COOLING CONTRACTURE, AND RYANODINE BINDING

To study the mechanisms of cardiac dysfunction in experimental diabete s, adult rat cardiomyocyte shortening (measured with a video edge-dete ctor system), the sarcoplasmic reticulum (SR) Ca2+ content [assessed b y rapid-cooling contracture (RCC) and caffeine contracture (CC)] was e xamined. Ryanodine binding to the SR Ca2+-release channel of myocardiu m homogenate was also studied. Myocytes from diabetic rats showed depr essed shortening (44% decrease compared with controls), reduced maximu m rates of shortening and relengthening (58 and 56% decrease, respecti vely), and prolonged time to peak shortening (47% increase). RCCs and CCs from diabetic cells were 68 and 75% of the control values, respect ively. Most of these cardiomyocyte abnormalities were corrected by dai ly insulin treatment in the diabetic rats. Ryanodine binding parameter s indicated that the number of high-affinity binding sites was decreas ed in diabetic hearts. These data suggest that changes in contractile parameters as measured in diabetic myocytes are in good agreement with data obtained from intact heart or cardiac tissue preparations. Decre ased SR Ca2+ content and reduced ryanodine binding sites indicate that the SR functions of storage and release of Ca2+ were depressed. This consequently may cause depressed contraction in diabetic hearts.