Cholinergic regulation of epithelial Na+ channel (ENaC) in alveolar type 2 cells.

Abstract

We and others have shown that epithelial Na+ channels (ENaC) in alveolar type 2 (AT2) cells are activated by β2 agonists, steroid hormones, elevated oxygen tension and by dopamine. Acetylcholine (Ach) receptors in bronchial smooth muscle are well known therapeutic targets in certain respiratory diseases, but there have been few reports on whether cholinergic agonists alter sodium transport in airway epithelial cells; therefore we investigated how cholinergic receptors regulate ENaC activity in primary cultures of rat AT2 cells and found that muscarinic agonists such as carbachol and oxotremorine activate ENaC. Rat AT2 cells were isolated by elastase treatment and were placed in primary culture. Cell attached‐patch clamp recording were used to investigate ENaC activities measured as the number of channels per patch times the open probability, NPo.Results of western blotting suggested M1 and M2 receptors were present in rat AT2 cells, but nicotinic receptors were not. Carbachol and oxotremorine increased NPo of ENaC in a dose‐dependent manner but nicotine did not. Atropine almost completely blocked ENaC activation by carbachol or oxotremorine.Our results showed that ENaC can be activated in rat AT2 cells by muscarinic agonists acting through M1 and M2 cholinergic receptors.