Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that when 
phosphorylated at Ser16 by PKA and/or at Thr17 by CaMKII increases the affinity 
of the SR Ca2+ pump for Ca2+. PLB is therefore, a critical regulator of SR 
function, myocardial relaxation and myocardial contractility. The present study 
was undertaken to examine the status of PLB phosphorylation after ischemia and 
reperfusion and to provide evidence about the possible role of the 
phosphorylation of Thr17 PLB residue on the recovery of contractility and 
relaxation after a period of ischemia. Experiments were performed in Langendorff 
perfused hearts from Wistar rats. Hearts were submitted to a protocol of global 
normothermic ischemia and reperfusion. The results showed that (1) the 
phosphorylation of Ser16 and Thr17 residues of PLB increased at the end of the 
ischemia and the onset of reperfusion, respectively. The increase in Thr17 
phosphorylation was associated with a recovery of relaxation to preischemic 
values. This recovery occurred in spite of the fact that contractility was 
depressed. (2) The reperfusion-induced increase in Thr17 phosphorylation was 
dependent on Ca2+ entry to the cardiac cell. This Ca2+ influx would mainly occur 
by the coupled activation of the Na+ / H+ exchanger and the Na+ / Ca2+ exchanger 
working in the reverse mode, since phosphorylation of Thr17 was decreased by 
inhibition of these exchangers and not affected by blockade of the L-type Ca2+ 
channels. (3) Specific inhibition of CaMKII by KN93 significantly decreased 
Thr17 phosphorylation. This decrease was associated with an impairment of 
myocardial relaxation. The present study suggests that the phosphorylation of 
Thr17 of PLB upon reflow, may favor the full recovery of relaxation after 
ischemia.