MODIFICATION OF ISCHEMIA-REPERFUSION-INDUCED CHANGES IN CARDIAC SARCOPLASMIC-RETICULUM BY PRECONDITIONING

To examine the effects of ischemic preconditioning on ischemia-reperfu sion-induced changes in the sarcoplasmic reticulum (SR) function, isol ated rat hearts were either perfused with a control medium for 30 min or preconditioned with three episodes of 5-min ischemia and 5-min repe rfusion before sustained ischemia for 30 min followed by reperfusion f or 30 min was induced. Preconditioning itself depressed cardiac functi on (left ventricular developed pressure, peak rate of contraction, and peak rate of relaxation) and SR Ca2+-release and -uptake activities a s well as protein content and Ca2+/calmodulin-dependent protein kinase (CaMK) phosphorylation of Ca2+-release channels by 25-60%. Global isc hemia for 30 min produced marked depressions in SR Ca2+-release and -u ptake activities as well as SR Ca2+-pump protein content in control he arts; these changes were significantly attenuated by preconditioning. Compared with the control preparations, preconditioning improved the r ecovery of cardiac function and SR Ca-2+-release and -uptake activitie s as well as Ca-2+-release channel and Ca2+-pump protein contents in t he ischemic-reperfused hearts. Unlike the protein kinase A-mediated ph osphorylation in SR membranes, the CaMK-mediated phosphorylations at C a2+-release channels, Ca2+ pump, and phospholamban were depressed in t he ischemic hearts; these changes were prevented by preconditioning. T hese results indicate that ischemic preconditioning may exert benefici al effects on ischemia-reperfusion-induced alterations in SR function by preventing changes in Ca2+-release channel and Ca2+-pump protein co ntents in the SR membrane.