Na+-K+-ATPase alpha 2-isoform expression in guinea pig hearts during transition from compensation to decompensation

Disturbance in ionic gradient across sarcolemma may lead to arrhythmias. Be cause Na+-K+-ATPase regulates intracellular Na+ and K+ concentrations, and therefore intracellular Ca2+ concentration homeostasis, our aim was to dete rmine whether changes in the Na+-K+-ATPase alpha-isoforms in guinea pigs du ring transition from compensated (CLVH) to decompensated left ventricular h ypertrophy (DLVH) were concomitant with arrhythmias. After 12- and 20-mo ao rtic stenosis, CLVH and DLVH were characterized by increased mean arterial pressure (30% and 52.7%, respectively). DLVH differed from CLVH by signific antly increased end-diastolic pressure (34%), decreased sarco( endo) plasmi c reticulum Ca2+-ATPase (-75%), and increased Na+/Ca2+ exchanger (25%) mRNA levels and by the occurrence of ventricular arrhythmias. The alpha-isoform (mRNA and protein levels) was significantly lower in DLVH (2.2 +/- 0.2- an d 1.4 +/- 0.15- fold, respectively, vs. control) than in CLVH (3.5 +/- 0.4- and 2.2 +/- 0.13-fold, respectively) and was present in sarcolemma and T t ubules. Changes in the levels of alpha(1)- and alpha(3)-isoform in CLVH and DLVH appear physiologically irrelevant. We suggest that the increased leve l of alpha(2)-isoform in CLVH may participate in compensation, whereas its relative decrease in DLVH may enhance decompensation and arrhythmias.