Hormonal and neurogenic control of Na-K-ATPase and myosin isoforms in neonatal rat cardiac myocytes.
In the rat heart there is a postnatal switch in the expression of isoforms of both Na-K-ATPase and myosin heavy chain (MHC). Here we investigated factors controlling isoform changes in cultures of neonatal cardiomyocytes. In serum-free medium, the compositions of either Na-K-ATPase or MHC isoforms resembled the neonatal phenotype. Thyroid hormone induced the MHC isoform switch but increased expression of all Na-K-ATPase isoforms to various extents. Dexamethasone failed to induce the MHC 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 alpha 2 protein was not predicted by studies of mRNA levels. 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. Expression of Na-K-ATPase alpha 2 was significantly upregulated when cardiomyocytes were cocultured with sympathetic neurons from superior cervical ganglia, without changes in the MHC isoforms. Thus innervation is postulated to play a specific role in modulating Na-K-ATPase gene expression.
Arystarkhova
E
E
Laboratory of Membrane Biology, Massachusetts General Hospital, Charlestown 02129, USA.
Sweadner
K J
KJ
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001790:Blood Physiological Phenomena; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D007536:Isomerism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology
D005938:Glucocorticoids; D006728:Hormones; D007527:Isoenzymes; D014284:Triiodothyronine; D003907:Dexamethasone; D009218:Myosins; D000254:Sodium-Potassium-Exchanging ATPase