Intermittent high-altitude (IHA)
hypoxia-induced cardioprotection against
ischemia-reperfusion (I/R) injury is associated with the preservation of sarcoplasmic reticulum (SR) function. Although Ca(2+)/
calmodulin (CaM)-dependent
protein kinase II (
CaMKII) and
phosphatase are known to modulate the function of cardiac SR under physiological conditions, the status of SR
CaMKII and
phosphatase during I/R in the hearts from IHA hypoxic rats is unknown. In the present study, we determined SR and cytosolic
CaMKII activity during preischemia and I/R (30 min/30 min) in perfused hearts from normoxic and IHA hypoxic rats. The left ventricular contractile recovery, SR
CaMKII activity as well as phosphorylation of
phospholamban at Thr(17), and Ca(2+)/CaM-dependent SR Ca(2+)-uptake activity were depressed in the I/R hearts from normoxic rats, whereas these changes were prevented in the hearts from IHA hypoxic rats. Such beneficial effects of IHA
hypoxia were lost by treating the hearts with a specific
CaMKII inhibitor,
KN-93. I/R also depressed cytosolic
CaMKII and SR
phosphatase activity, but these alterations remained unchanged in IHA hypoxic group. Furthermore, we found that the autophosphorylation at Thr(287), which confers Ca(2+)/CaM-independent activity, was not altered by I/R in both groups. These findings indicate that preservation of SR
CaMKII activity plays an important role in the IHA
hypoxia-induced cardioprotection against I/R injury via maintaining SR Ca(2+)-uptake activity.