Levitan E S, Hershman K M, Sherman T G, Takimoto K
Department of Pharmacology, University of Pittsburgh, PA 15261, USA.
Neuropharmacology. 1996;35(7):1001-6.
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.
激素可能通过调节钾离子通道基因表达对兴奋性产生长期影响。先前的研究表明，给肾上腺切除的大鼠注射地塞米松（一种糖皮质激素受体激动剂），可迅速诱导心脏心室中Kv1.5钾离子通道的表达。在此，采用核糖核酸酶保护试验和Northern印迹法来检测地塞米松作用的细胞类型特异性，并测试Kv1.5基因表达是否可受生理刺激调节。我们发现，中枢神经系统中Kv1.5信使核糖核酸（mRNA）的表达在下丘脑中最高。然而，给肾上腺切除的大鼠注射地塞米松，并不会影响下丘脑或肺中Kv1.5 mRNA的水平。相反，在骨骼肌和垂体中可见Kv1.5 mRNA显著上调。在用体内地塞米松处理后，在分离的心室心肌细胞中也发现Kv1.5信使增加。最后，结果表明，完整大鼠的冷应激可显著增加心脏Kv1.5 mRNA的表达。我们得出结论，地塞米松对Kv1.5基因的诱导具有组织特异性。此外，我们的结果表明，应激可能通过糖皮质激素作用来增加心室心肌细胞中Kv1.5基因的表达。因此，钾离子通道基因表达可受生理和药理刺激的影响。
