DEXAMETHASONE AND STRESS UP-REGULATE KV1.5 K-EXPRESSION IN RAT VENTRICULAR MYOCYTES( CHANNEL GENE)

Hormones may produce long-term effects on excitability by regulating K + channel gene expression. Previous studies demonstrated that administ ration of dexamethasone, a glucocorticoid receptor agonist, to adrenal ectomized rats, rapidly induces Kv1.5 K+ channel expression in the ven tricle of the heart. Here, RNase protection assays and Northern blots are used to examine the cell type specificity of dexamethasone action and to test whether Kv1.5 gene expression can be regulated by a physio logical stimulus. We show that Kv1.5 mRNA expression in the central ne rvous system is highest in the hypothalamus. However, dexamethasone tr eatment of adrenalectomized rats fails to affect Kv1.5 mRNA levels in hypothalamus or lung. In contrast, dramatic upregulation of Kv1.5 mRNA is seen in skeletal muscle and pituitary. Increased Kv1.5 message als o is found in isolated ventricular cardiomyocytes following in vivo tr eatment with dexamethasone. Finally, it is shown that cold stress of i ntact rats significantly increases cardiac Kv1.5 mRNA expression. We c onclude that dexamethasone induction of the Kv1.5 gene is tissue-speci fic. Furthermore, our results suggest that stress may act via glucocor ticoids to increase Kv1.5 gene expression in ventricular cardiomyocyte s. Hence, K+ channel gene expression can be influenced by physiologica l and pharmacological stimuli. Copyright (C) 1996 Elsevier Science Ltd