Na+-K+-ATPase α2-isoform expression in guinea pig hearts during transition from compensation to decompensation

Abstract

Disturbance in ionic gradient across sarcolemma may lead to arrhythmias. Because Na+-K+-ATPase regulates intracellular Na+ and K+concentrations, and therefore intracellular Ca2+concentration homeostasis, our aim was to determine whether changes in the Na+-K+-ATPase α-isoforms in guinea pigs during transition from compensated (CLVH) to decompensated left ventricular hypertrophy (DLVH) were concomitant with arrhythmias. After 12- and 20-mo aortic stenosis, CLVH and DLVH were characterized by increased mean arterial pressure (30% and 52.7%, respectively). DLVH differed from CLVH by significantly increased end-diastolic pressure (34%), decreased sarco(endo)plasmic reticulum Ca2+-ATPase (−75%), and increased Na+/Ca2+ exchanger (25%) mRNA levels and by the occurrence of ventricular arrhythmias. The α-isoform (mRNA and protein levels) was significantly lower in DLVH (2.2 ± 0.2- and 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 tubules. Changes in the levels of α1- and α3-isoform in CLVH and DLVH appear physiologically irrelevant. We suggest that the increased level of α2-isoform in CLVH may participate in compensation, whereas its relative decrease in DLVH may enhance decompensation and arrhythmias.