Pulmonary surfactant proteins insert cation-permeable channels in planar bilayers

Pulmonary surfactant, a mixture of lipids and proteins, promotes lung venti lation by reduction of surface tension at air-fluid interfaces. Exogenous s urfactants containing hydrophobic proteins induce biological effects in lun gs that are not fully explained by reduction of surface tension and are not induced by surfactants lacking proteins. We hypothesized that hydrophobic proteins from surfactant insert in membranes to induce channel activities t hat contribute to the observed biological effects of surfactant. To test fo r channel insertion by surfactant, planar lipid bilayers were monitored ele ctrophysiologically in the presence of either intact pulmonary surfactant o r extracted surfactant proteins reconstituted with phospholipids or directl y added to bilayer lipids prior to membrane casting. In this in vitro model , both intact surfactant and extracted surfactant proteins initiated gated channel activities with slope conductances averaging 40 pS. Observed revers al potentials confirmed monovalent cation conductance, and conductance of s maller monovalent cations was selective. Voltage dependence of channel open ings and rectification of channel current were not observed. These results confirm that hydrophobic surfactant proteins induce channel-mediated transp ort in artificial membranes. We speculate that pulmonary surfactants, in ad dition to reducing surface tension at air-fluid interfaces, initiate physio logical and therapeutic effects in lung by cation channel insertion at expo sed epithelial membranes. (C) 2000 Academic Press.