Intracellular Ca2+ and adrenergic responsiveness of cardiac myocytes in streptozotocin-induced diabetes

1. The contractile function of diabetic hearts is impaired. In addition, th e responsiveness of diabetic cardiac muscle to sympathetic stimulation is a ltered, Previous studies have revealed a depressed response to beta-adrenoc eptor stimulation; however, the response to alpha-adrenoceptor activation r emains controversial. Because alpha- and beta-adrenoceptor agonists increas e cardiac contractility, largely through increased mobilization of intracel lular Ca2+, the aim of the present study was to investigate the effects of alpha- and beta-adrenoceptor stimulation on intracellular Ca2+ handling in cardiac myocytes from streptozotocin-induced diabetic rats. 2, Intracellular Ca2+ was measured using fura-2, Under basal conditions (27 degrees C, 2.5 mmol/L extracellular [Ca2+], 0.3 Hz stimulation), there was no significant difference in resting or peak Ca2+ levels between control a nd diabetic cardiomyocytes. However, the time course of the intracellular C a2+ transient was significantly prolonged in cells from diabetic hearts. 3, The beta-adrenoceptor agonist orciprenaline (at 10(-7) and 10(-6) mol/L) increased the amplitude of the Ca2+ transient in both groups; however, the extent of potentiation was less in diabetic compared with control cardiomy ocytes. Orciprenaline decreased the duration of the transient to the same e xtent in both groups. 4, The alpha-adrenoceptor agonist phenylephrine (at 10(-7) and 10(-6) mol/L ) had no effect on the Ca2+ transient in control myocytes but caused a sign ificant concentration-dependent increase in its amplitude in diabetic cardi omyocytes, Phenylephrine had no effect on the time course of the transient in either group, 5, These results demonstrate differential effects of insulin-dependent diab etes on the responsiveness of cardiomyocytes to alpha- and beta-adrenocepto r stimulation, The heightened response to alpha-adrenoceptor stimulation ob served in diabetic cardiomyocytes may partly compensate for the diminished myocardial beta-adrenoceptor response.