EFFECTS OF BETA-ADRENOCEPTOR STIMULATION ON CONTRACTILITY, [CA2+](I),AND CA2+ CURRENT IN DIABETIC RAT CARDIOMYOCYTES

The mechanism of the diminished inotropic response to beta-adrenocepto r stimulation in diabetic hearts was studied in enzymatically isolated diabetic rat ventricular myocytes in comparison with age-matched cont rols. The increases in contractions and intracellular Ca2+ concentrati on ([Ca2+](i)) transients produced by isoproterenol were markedly dimi nished in diabetic myocytes. The inotropic and [Ca2+](i) responses to forskolin and dibutyryl cAMP (DBcAMP) were also reduced. No significan t difference was found in the stimulating effects of isoproterenol, fo rskolin, and DBcAMP on the L-type Ca2+ current (I-Ca) between control and diabetic myocytes. The rise of [Ca2+](i) in response to rapid caff eine application, an index of sarcoplasmic reticulum (SR) Ca2+ content , was significantly decreased in diabetic myocytes. Isoproterenol, for skolin, and DBcAMP enhanced this [Ca2+](i) response to caffeine in con trol myocytes more markedly than in diabetic myocytes. The changes in the isoproterenol responses observed in diabetic myocytes were prevent ed by insulin therapy. We conclude that 1) diabetes causes an impairme nt of the contractile and [Ca2+](i) responses of cardiac myocytes when stimulated at both beta-adrenoceptors and the postreceptor level with out affecting the I-Ca response and 2) altered SR functions of uptake and/or release of Ca2+ may primarily contribute to the diminished beta -adrenergic response.