Role and regulation of lung Na,K-ATPase

The recognition that pulmonary edema is cleared from the alveolar airspace by active Na+ transport has led to studies of the role and regulation of al veolar epithelial Na,K-ATPases. In the lung these heterodimers are predomin antly composed of alpha1 and beta1-subunits and are located on the basolate ral aspect of alveolar type 2 epithelial cells (AT2). Working with apically positioned epithelial Na+ channels they generate a transepithelial osmotic gradient which causes the movement of fluid out of the alveolar airspace. Accumulating data indicates that in some forms of pulmonary edema alveolar Na,K-ATPases function is reduced suggesting that pulmonary edema may be due , in part, to impairment of edema clearance mechanisms. Other studies sugge st that Na,K-ATPase dysfunction or inhibition may contribute to airway reac tivity. It is now recognized that lung Na,K-ATPases are positively regulate d by glucocorticoids, aldosterone, catecholamines and growth hormones. Thes e findings have led to investigations that show that enhancement of Na,K-AT Pase function can accelerate pulmonary edema clearance in vitro, in normal and injured animal lungs in vivo, and in human lung explants. This review f ocuses on Na,K-ATPase data from lung and lung cell experiments that highlig ht the importance of Na,K-ATPases in airway reactivity and in maintaining a dry alveolar airspace. Review of data that suggests that there may be a ro le for therapeutic modulation of alveolar Na,K-ATPases for the purpose of t reating patients with respiratory failure are also included.