AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 293: H3584-H3592, 2007. First published September 21, 2007; doi:10.1152/ajpheart.00619.2007
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Sex-related effects on diabetes-induced alterations in calcium release in the rat heart

Nazmi Yaras,1 Erkan Tuncay,1 Nuhan Purali,2 Babur Sahinoglu,2 Guy Vassort,3 and Belma Turan1

1Departments of Biophysics, Faculty of Medicine, Ankara University, and 2Hacettepe University, Ankara, Turkey; and 3Institut National de la Santé et de la Recherche Médicale U637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France

Submitted 28 May 2007 ; accepted in final form 19 September 2007

The present study was designed to determine whether the properties of local Ca2+ release and its related regulatory mechanisms might provide insight into the role of sex differences in heart functions of control and streptozotocin-induced diabetic adult rats. Left ventricular developed pressure, the rates of pressure development and decay (±dP/dt), basal intracellular Ca2+ level ([Ca2+]i), and spatiotemporal parameters of [Ca2+]i transients were found to be similar in male and female control rats. However, spatiotemporal parameters of Ca2+ sparks in cardiomyocytes isolated from control females were significantly larger and slower than those in control males. Diabetes reduced left ventricular developed pressure to a lower extent in females than in males, and the diabetes-induced depressions in both +dP/dt and –dP/dt were less in females than in males. Diabetes elicited a smaller reduction in the amplitude of [Ca2+]i transients in females than in males, a smaller reduction in sarcoplasmic reticulum-Ca2+ load, and less increase in basal [Ca2+]i. Similarly, the elementary Ca2+ events and their control proteins were clearly different in both sexes, and these differences were more marked in diabetes. Diabetes-induced depression of the Ca2+ spark amplitude was significantly less in females than in matched males. Levels of cardiac ryanodine receptors (RyR2) and FK506-binding protein 12.6 in control females were significantly higher than those shown in control males. Diabetes induced less RyR2 phosphorylation and FK506-binding protein 12.6 unbinding in females. Moreover, total and free sulfhydryl groups were significantly less reduced, and PKC levels were less increased, in diabetic females than in diabetic males. The present data related to local Ca2+ release and its related proteins describe some of the mechanisms that may underlie sex-related differences accounting for females to have less frequent development of cardiac diseases.

calcium sparks; calcium transient; ryanodine receptors; Type 1 diabetes; excitation-contraction coupling



Address for reprint requests and other correspondence: B. Turan, Dept. of Biophysics, School of Medicine, Ankara Univ., Ankara, Turkey (e-mail: belma.turan{at}medicine.ankara.edu.tr)







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