DEPRESSED [CA2+](I) RESPONSES TO ISOPROTERENOL AND CAMP IN ISOLATED CARDIOMYOCYTES FROM EXPERIMENTAL DIABETIC RATS

Experimentally, diabetic rat hearts are characterized by diminished re sponses to beta-adrenergic stimulation. Among the aberrant responses a re diminished beta-adrenoceptor number and depressed contractile prote in activity. In this study, intracellular Ca2+ concentration ([Ca2+](i )) was determined by microfluorescence in response to beta-adrenergic stimulation to understand the basis for the changes in the beta-adrene rgic pathway in diabetic myocardium. In quiescent myocytes, isoprotere nol caused a decrease in [Ca2+](i), which was blocked by timolol and t hapsigargin. This suggests that the beta-agonist-induced [Ca2+](i) cha nges are mediated, in part, by sarcoplasmic reticulum Ca-adenosinetrip hosphatase. Diabetic myocytes showed a blunted response to isoproteren ol, which was reversed by insulin treatment. In electrically stimulate d myocytes, isoproterenol and 8-bromo-adenosine 3',5'-cyclic monophosp hate (cAMP) increased [Ca2+](i) and contraction in a concentration-dep endent manner. Electrically stimulated diabetic myocytes demonstrated a depressed maximum [Ca2+](i) response to isoproterenol and 8-bromo-cA MP without a change in sensitivity. These data suggest that in additio n to alterations in beta-adrenoceptor function there are postreceptor defects in diabetic myocardium that may impair the regulation of [Ca2](i) in diabetic myocardium.