Calcium binding to sarcolemmal membranes isolated from diabetic rat heart

56 CALCIUM BINDING TO SARCOLEMMAL MEMBRANES ISOLATED FROM DIABETIC RAT HEART. Grant N. Pierce, Michael J.B. Kutryk and Naranjan S. Dhalla. University of Manitoba, Winnipeg, Canada R3E OW3 This study was conducted to determine the possible involvement of a sarcolemmal membrane defect in the diabetic cardiomyopathy. Streptozotocin-induced diabetic rats were sacrificed 8 weeks after injection (65 mg/kg body weight) and sarcolemmal (SL) membranes were isolated from cardiac tissue by the hypotonic shock-LiBr procedure. ATP-independent Ca*+ binding (1.25 mM and 0.05 mM) was found to be depressed in cardiac SL membranes from diabetic rats in comparison to control animals, Sialic acid content of SL from diabetic rats was also significantly depressed. Neuraminidase treatment of SL membranes significantly reduced Ca*+ binding to control preparations by 37% but had no effect on experimental preparations. However, no difference in SL sialyltransferase activity could be detected between the groups. Examination of phospholipid composition of SL membranes revealed increased lysophosphatidylcholine and decreased phosphatidylethanolamine and phosphatidylglycerol content in SL from diabetic rats. All other phospholipids were unaltered. In contrast, SL Ca*+-dependent ATPase activity was increased in SL from diabetic rats in comparison to control. This study suggests alterations in cardiac SL membranes during diabetes with respect to its Ca*+-related activities. Such alterations in SL may contribute to the development of the diabetic cardiomyopathy and may partly explain depressed cardiac function. (Supported by a grant from the Medical Research Council of Canada).

CATECHOLAMINE TACHYARRHYTHMIAS INHIBITED BY MYOCARDIAL ISCHEMIA. Thomas Podzuweit, Karl Heinz Binz and Wolfgang Schaper. Max-Planck-Institute, Bad Nauheim, West Germany These experiments were designed to test the hypothesis that early post coronary ligation arrhythmias and ventricular fibrillation are due to the combined action of augmented extracellular potassium and liberation of endogenous catecholamines in the ischemic area. In open-chest pigs shallow (l-5 mm) intramyocardial infusions (10 wl/min) of a mixture of norepinephrine (10 PM), CaC12 (2.5 mM) and NaCl (150 mM) consistently produced persistent ventricular tachycardia. In contrast, arrhythmias could not be induced by intramyocardial infusion of KC1 (up to 100 mM). Infusion of KC1 (lo-30 mM) combined with the norepinephrine-Ca2+ solution inhibited the induction of ventricular tachycardia. During ventricular tachycardia produced by norepinephrine-Ca2+ infusion tachycardia was stopped within lo-30 s by occluding the coronary artery supplying the infusion area. This ischemic effect was readily reversible by coronary reperfusion. At the time that the

norepinephrine-Ca2+ tachycardia ischemia, the ventricle could

was stopped by myocardial still be electrically paced

through the infusion needle. In conclusion, these results indicate that ventricular tachycardia produced by adrenergic overstimulation is inhibited by augmented extracellular potassium concentration and by myocardial ischemia. The interruption of ventricular tachycardia by ischemia was probably not due to a conduction block.