HORMONAL AND NEUROGENIC CONTROL OF NA-K-ATPASE AND MYOSIN ISOFORMS INNEONATAL RAT CARDIAC MYOCYTES

In the rat heart there is a postnatal switch in the expression of isof orms of both Na-K-ATPase and myosin heavy chain (MHC). Here we investi gated factors controlling isoform changes in cultures of neonatal card iomyocytes. In serum-free medium, the compositions of either Na-E-ATPa se or MHC isoforms resembled the neonatal phenotype. Thyroid hormone i nduced the MHC isoform switch but increased expression of all Na-K-ATP ase isoforms to various extents. Dexamethasone failed to induce the MH C switch and inhibited Na-K-ATPase alpha(1) isoform expression without inducing the other isoforms. With both hormones, the adult phenotype for both MHC and Na-K-ATPase was seen but with low Na-K-ATPase alpha(2 ). The paucity of at protein was not predicted by studies of mRNA leve ls. In serum, there was a gradual decline of Na-K-ATPase alpha(3) and the appearance of alpha(2), but again at a relatively low level. Expre ssion of Na-K-ATPase alpha(2) was significantly upregulated when cardi omyocytes were cocultured with sympathetic neurons from superior cervi cal ganglia, without changes in the MHC isoforms. Thus innervation is postulated to play a specific role in modulating Na-K-ATPase gene expr ession.