pH-regulated chloride secretion in fetal lung epithelia

The fetal lung actively transports chloride across the airway epithelium. C lC-2, a pH-activated chloride channel, is highly expressed in the fetal lun g and is located on the apical surface of the developing respiratory epithe lium. Our goal was to determine whether acidic pH could stimulate chloride secretion in fetal rat distal lung epithelial cells mounted in Ussing chamb ers. A series of acidic solutions stimulated equivalent short-circuit curre nt (I-eq) from a baseline of 28 +/- 4.8 (pH 7.4) to 70 +/- 5 (pH 6.2), 114 +/- 12.8 (pH 5.0), and 164 +/- 19.2 (pH 3.8) mu A/cm(2). These changes in I -eq were inhibited by 1 mM cadmium chloride and did not result in large cha nges in [H-3]mannitol paracellular flux. Immunofluorescent detection by con focal microscopy revealed that ClC-2 is expressed along the luminal surface of polarized fetal distal lung epithelial cells. These data suggest that t he acidic environment of the fetal lung fluid could activate chloride chann els contributing to fetal lung fluid production and that the changes in I-e q seen in these Ussing studies may be due to stimulation of ClC-2.