Dexamethasone and stress upregulate Kv1.5 K+ channel gene expression in rat ventricular myocytes.
Hormones may produce long-term effects on excitability by regulating K+ channel gene expression. Previous studies demonstrated that administration of dexamethasone, a glucocorticoid receptor agonist, to adrenalectomized rats, rapidly induces Kv1.5 K+ channel expression in the ventricle of the hear. 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 physiological stimulus. We show that Kv1.5 mRNA expression in the central nervous system is highest in the hypothalamus. However, dexamethasone treatment 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 also found in isolated ventricular cardiomyocytes following in vivo treatment with dexamethasone. Finally, it is shown that cold stress of intact rats significantly increases cardiac Kv1.5 mRNA expression. We conclude that dexamethasone induction of Kv1.5 gene is tissue-specific. Furthermore, our results suggest that stress may act via glucocorticoids to increase Kv1.5 gene expression in ventricular cardiomyocytes. Hence, K+ channel gene expression can be influenced by physiological and pharmacological stimuli.
Levitan
E S
ES
Department of Pharmacology, University of Pittsburgh, PA 15261, USA.
Hershman
K M
KM
Sherman
T G
TG
Takimoto
K
K
D000315:Adrenalectomy; D000818:Animals; D015152:Blotting, Northern; D003080:Cold Temperature; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006352:Heart Ventricles / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects; D051666:Kv1.5 Potassium Channel; D010902:Pituitary Gland / Q000737:chemistry / Q000187:drug effects; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D003907:Dexamethasone