Phospholamban in ischemia and reperfusion:insights from transgenic animals.

SAID M, MUNDIÑA-WEILENMANN C, VITTONE L, FERRERO P, KRANIAS E, MATTIAZZI A.

La Plata

Congreso; X Meeting of the International Society for Heart Research. Latin American; 2002

International Society for Heart Research

25  PHOSPHOLAMBAN IN ISCHEMlA AND REPERFUSION:INSIGHTS FROM TRANSGENIC ANIMALS. Matilde Said’, Cecilia Mundiña-Weilenmann’, Leticia Vittone’, Paola Ferrero’, Evangelia Kranias*, Alicia Mattiazzi’. ’Centro de lnvestigaciones Cardiovasculares, Facultad de Medicina, La Plata, Argentina and *University of Cincinnati, Cincinnati OH, USA.   Phosphorylation of the sarcoplasmic reticulum (SR) protein phospholamban (PLB) at Se16 by PKA and at Tht’ by CaMKII, increases the SR Ca uptake and myocardial relaxation and contractility. In the rat heart, ischemia and reperfusion injury increased the phosphorylation of both PLB sites: Ser16 phosphorylation was increased at the end of ischemia. This phosphorylation was dependent on beta- adrenergic cascade stimulation. Th+’ phosphorylation was increased at the onset of reperfusion. This phosphorylation was dependent on Ca influx through the NalCa exchanger (J Mol Cell Cardiol 34: 39-50, 2002). The present study examined the possible role of PLB phosphorylation residues on the recovery of contractility after a period of ischemia, in Langendorff perfused hearts from transgenic mice models. These models express wild-Tpe PLB (WT), the Se16 –Ala mutant (S16A) or the Thr 17-Ala mutant (T17A) in the cardiac compartment of the PLB knockout mouse. Hearts were submitted to global normothermic ischemia (12 min) followed by reperfusion. After ischemia left ventricular developed pressure increased to 37.2±8.1% (n=8) of preischemic values in WT hearts. This recovery was significantly lower in both mutant hearts (S16A, 15.4±5.0%, n=l0 and T17A, 14.8±5.8%, n=6) with respect to WT. The results suggest that both PLB residues participate in the recovery of contractility during reperfusion after ischemia.