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INTRACELLULAR Ca 2+ AND ADRENERGIC RESPONSIVENESS OF CARDIAC MYOCYTES IN STREPTOZOTOCIN‐INDUCED DIABETES
Author(s) -
Ha Tuyen,
Kotsanas George,
Wendt Igor
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03040.x
Subject(s) - phenylephrine , medicine , endocrinology , intracellular , stimulation , myocyte , agonist , contractility , chemistry , cardiac transient outward potassium current , streptozotocin , diabetes mellitus , receptor , patch clamp , biochemistry , blood pressure
1. The contractile function of diabetic hearts is impaired. In addition, the responsiveness of diabetic cardiac muscle to sympathetic stimulation is altered. Previous studies have revealed a depressed response to β‐adrenoceptor stimulation; however, the response to α‐adrenoceptor activation remains controversial. Because α‐ and β‐adrenoceptor agonists increase cardiac contractility, largely through increased mobilization of intracellular Ca 2+ , the aim of the present study was to investigate the effects of α‐ and β‐adrenoceptor stimulation on intracellular Ca 2+ handling in cardiac myocytes from streptozotocin‐induced diabetic rats. 2. Intracellular Ca 2+ was measured using fura‐2. Under basal conditions (27°C, 2.5 mmol/L extracellular [Ca 2+ ], 0.3 Hz stimulation), there was no significant difference in resting or peak Ca 2+ levels between control and diabetic cardiomyocytes. However, the time course of the intracellular Ca 2+ transient was significantly prolonged in cells from diabetic hearts. 3. The β‐adrenoceptor agonist orciprenaline (at 10 − 7 and 10 − 6 mol/L) increased the amplitude of the Ca 2+ transient in both groups; however, the extent of potentiation was less in diabetic compared with control cardiomyocytes. Orciprenaline decreased the duration of the transient to the same extent in both groups. 4. The α‐adrenoceptor agonist phenylephrine (at 10 − 7 and 10 − 6 mol/L) had no effect on the Ca 2+ transient in control myocytes but caused a significant concentration‐dependent increase in its amplitude in diabetic cardiomyocytes. Phenylephrine had no effect on the time course of the transient in either group. 5. These results demonstrate differential effects of insulin‐ dependent diabetes on the responsiveness of cardiomyocytes to α‐ and β‐adrenoceptor stimulation. The heightened response to α‐adrenoceptor stimulation observed in diabetic cardiomyocytes may partly compensate for the diminished myocardial β‐adrenoceptor response.