| Abstract | dc.description.abstract | We have previously demonstrated that brief episodes of tachycardia prior to a prolonged occlusion of a coronary artery, followed by reperfusion, substantially reduce the infarct size. Adenosine receptors and mitochondrial ATP-dependent K+ channels mediate this effect. Since preconditioning can be induced or reverted by maneuvers that increase or decrease [Ca2+](i), respectively, and tachycardia increases [Ca2+](i) we studied the participation of sarcoplasmic reticulum and Ca2+ in the preconditioning effect of tachycardia. We measured the effect of ischemia and tachycardia on Ca2+ uptake and release by sarcoplasmic reticulum vesicles isolated from left ventricular canine myocardium. Myocardial ischemia increased Ca2+-release rate constants and decreased both the initial rates of Ca2+ uptake and [H-3]-ryanodine binding by sarcoplasmic reticulum. In addition, ischemia induced a decrease in the pentameric form of phospholamban and in the content of ryanodine-receptor Ca2+-release channel protein. All these effects were reverted in hearts preconditioned with tachycardia. Furthermore, tachycardia by itself increased [H-3]-ryanodine binding, Ca2+-release rate constants and the protein levels of ryanodine-receptor Ca2+-release channels and the ATP-dependent Ca2+ pump. These results suggest that tachycardia preserves the integrity of the sarcoplasmic reticulum preventing the excess of release and the decrease of uptake of Ca2+ produced by ischemia, thereby avoiding cytosolic Ca2+ overload. This sarcoplasmic reticulum protection could partly explain the preconditioning effect of tachycardia. | en |
