Beta adrenergic agonists (βAA) have been shown to increase alveolar fluid clearance but the mechanism is unknown. Since βAA are known to stimulate adenylate cyclase, we investigated the presence of a cAMP-protein kinase A-dependent pathway for activation of sodium and water transport by distal lung epithelia. The patch-clamp technique was used to obtain single-channel recordings from the apical surface of rat type II (AT-II) cells in primary culture. The cation channel studied has a unitary conductance of 20.6±1.1 pS and a Na+/K+ selectivity of 0.97±0.07. Table 1 shows the change in open probability (Po) of channels in response to βAA and cAMP in the cell-attached patch-clamp configuration with each patch serving as its own control (See table below). The effect of terbutaline was blocked by propranolol (β-blocker)(Po control vs. propranolol 20 μM + terbutaline 20μM: 0.233±0.077 vs. 0.261±0.075, n=8, p=NS). The effect was also blocked by H-89 (PKA inhibitor)(Po control vs. H89 5μM + terbutaline 20 μM: 0.065±0.013 vs. 0.109±0.037, n=6, p=NS). AT-II cells responded to terbutaline with increased cAMP levels (cAMP fmol/mg protein; control 153±150, terbutaline 20 μM 1239.7±1406, n=6, p<.05). These observations confirm that βAA activate lung epithelial sodium transport via a cAMP PKA-mediated activation of amiloride-sensitive cation channels. βAA may have a beneficial role in lung conditions accompanied by pulmonary edema, and may accelerate fetal lung fluid clearance after birth.

Table 1 No caption available.