Cardiac Na+–H+Exchanger During Postnatal Development in the Rat: Changes in mRNA Expression and Sarcolemmal Activity

We examined Na+–H+exchanger isoform 1 (NHE-1) mRNA expression in ventricular myocardium and its correlation with sarcolemmal NHE activity in isolated ventricular myocytes, during postnatal development in the rat. The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA did not change in ventricular myocardium between 2 and 42 days after birth. Therefore, at seven time points within that age range, GAPDH expression was used to normalize NHE-1 mRNA levels, as determined by reverse transcription polymerase chain reaction analysis. There was a progressive five-fold reduction in NHE-1 mRNA expression in ventricular myocardium from 2 days to 42 days of age. As an index of NHE activity, acid efflux rates (JH) were determined in single neonatal (2–4-day-old) and adult (42-day-old) ventricular myocytes (n=16/group) loaded with the pH fluoroprobe carboxy-seminaphthorhodafluor-1. In HEPES-buffered medium, basal intracellular pH (pHi) was similar at 7.28±0.02 in neonatal and 7.31±0.02 in adult myocytes, but intrinsic buffering power was lower in the former age group. The rate at which pHirecovered from a similar acid load was significantly greater in neonatal than in adult myocytes (0.36±0.07v0.16±0.02 pH units/min at pHi=6.8). This was reflected by a significantly greaterJH(22±4v9±1 pmol/cm2/s at pHi=6.8), indicating greater sarcolemmal NHE activity in neonatal myocytes. The concomitant reductions in tissue NHE-1 mRNA expression and sarcolemmal NHE activity suggest that myocardial NHE-1 is subject to regulation at the mRNA level during postnatal development.