Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca2+ Homeostasis in Rat Heart

Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca 2+ Homeostasis in Rat Heart Nazmi Yaras 1 , Mehmet Ugur 1 , Semir Ozdemir 1 , Hakan Gurdal 2 , Nuhan Purali 3 , Alain Lacampagne 4 , Guy Vassort 4 and Belma Turan 1 1 Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey 2 Department of Pharmacology, School of Medicine, Ankara University, Ankara, Turkey 3 Department of Biophysics, School of Medicine, Hacettepe University, Ankara, Turkey 4 INSERM U-637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France Address correspondence and reprint requests to Dr. Belma Turan, Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey. E-mail: belma.turan{at}medicine.ankara.edu.tr Abstract The defects identified in the mechanical activity of the hearts from type 1 diabetic animals include alteration of Ca 2+ signaling via changes in critical processes that regulate intracellular Ca 2+ concentration. These defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channel (RyR2). The present study was designed to determine whether the properties of the Ca 2+ sparks might provide insight into the role of RyR2 in the altered Ca 2+ signaling in cardiomyocytes from diabetic animals when they were analyzed together with Ca 2+ transients. Basal Ca 2+ level as well as Ca 2+ -spark frequency of cardiomyoctes isolated from 5-week streptozotocin (STZ)-induced diabetic rats significantly increased with respect to aged-matched control rats. Ca 2+ transients exhibited significantly reduced amplitude and prolonged time courses as well as depressed Ca 2+ loading of sarcoplasmic reticulum in diabetic rats. Spatio-temporal properties of the Ca 2+ sparks in cardiomyocytes isolated from diabetic rats were also significantly altered to being almost parallel to the changes of Ca 2+ transients. In addition, RyR2 from diabetic rat hearts were hyperphosphorylated and protein levels of both RyR2 and FKBP12.6 depleted. These data show that STZ-induced diabetic rat hearts exhibit altered local Ca 2+ signaling with increased basal Ca 2+ level. RyR2, ryanodine receptor Ca release channel SR, sarcoplasmic reticulum STZ, streptozotocin Footnotes Accepted August 4, 2005. Received May 11, 2005. DIABETES