Halothane stimulates a Na+H+ antiporter involved in the regulation of intracellular pH in alveolar epithelial cells

Changes in intracellular pH (pHi) of alveolar type II (ATII) cells have bee n involved in the pathophysiology of pulmonary edema. ATII cells have evolv ed several ions transporters to regulate their pHi, including a Na+H+ antip orter. Because halothane alters the activity of ion transporters in various cells types, it may also affect the activity of this Na+H+ antiporter. Thi s study was performed 1) to characterize a Na+H+ antiporter in a model of A TII cells and 2) to investigate the effect of halothane on the activity of this antiporter. ATII cells were obtained from primary rat ATII cells trans fected with a mutant of simian virus SV40 large T antigen (SV40-T2), and th eir pHi was monitored using the pH-sensitive fluorescent probe 2'-7' (bis c arboxyethyl)5-(6')-carboxyfluorescein. We demonstrated in vitro that 1) a N a+H+ antiporter (apparent Km 6.8 +/- 3.4 mM, Vmax 0.0105 +/- 0.0013 Delta U pHi/s) regulates the pH of SV40-T2 cells and 2) at clinically relevant conc entrations (10(-3) to 10(-5) M) and for a short exposure duration (60 min), halothane enhances the activity of this antiporter. Because ATII cell acid ification has been associated with alterations in the alveolar epithelial b arrier, halothane-induced intracellular alkalinization might exhibit some p rotective effect in clinical situations, such as aspiration pneumonia. Impl ications: In vitro, halothane induces an intracellular alkalinization of pn eumocytes II via the activation of a Na+H+ antiporter. Because acidificatio n of these cells has been associated with alterations in the alveolar epith elial barrier, halothane might exhibit some protective effect in clinical s ituations, such as aspiration pneumonia.