Regulation of expression of the lung amiloride‐sensitive Na+ channel by steroid hormones

Molecular cloning of the amiloride‐sensitive Na+ channel has permitted analysis of the mechanisms of its stimulation by steroids. In rat lung cells in primary culture, where its mRNA has been detected, the activity of an amiloride‐sensitive channel, highly selective for Na+, is controlled by corticosteroids. Dexamethasone (0.1 microM) or aldosterone (1 microM) 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 synthetic specific agonists and antagonists for mineralo‐ and glucocorticoid 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 on both the amiloride‐sensitive Na+ current and the level of the mRNA for the Na+ channel protein, but potentiates the stimulatory effect of dexamethasone. The increase in Na+ channel activity observed in the lung around birth can thus be explained by a direct increase in transcription of the Na+ channel gene.