REGULATION OF EXPRESSION OF THE LUNG AMILORIDE-SENSITIVE NA-HORMONES(CHANNEL BY STEROID)

Molecular cloning of the amiloride-sensitive Na+ channel has permitted analysis of the mechanisms of its stimulation by steroids. In rat lun g cells in primary culture, where its mRNA has been detected, the acti vity of an amiloride-sensitive channel, highly selective for Na+, is c ontrolled by corticosteroids. Dexamethasone (0.1 mu M) or aldosterone (1 mu M) induced, after a minimum 10 h treatment, a large increase of the amiloride-induced hyperpolarization and of the amiloride-sensitive current. A parallel increase in the amount of the mRNA was observed. The corresponding gene is thus a target for steroid action. Using synt hetic specific agonists and antagonists for mineralo- and glucocortico id receptors, it has been shown that the steroid action on Na+ channel expression is mediated via glucocorticoid receptors. Triiodothyronine , known to modulate steroid action in several tissues, had no effect o n both the amiloride-sensitive Na+ current and the level of the mRNA f or the Na+ channel protein, but potentiates the stimulatory effect of dexamethasone. The increase in Na+ channel activity observed in the lu ng around birth can thus be explained by a direct increase in transcri ption of the Na+ channel gene.