Chloride secretion across distal airway epithelium: relationship to submucosal gland distribution

To evaluate the possible relationship between submucosal glands and transepithelial Cl- secretion, we compared the bioelectric properties of two distal airway regions: bronchioles, which contain few submucosal glands, and small bronchi, which contain numerous glands. Intact distal bronchi were dissected from the lungs of 4-8 wk old pigs and cannulated with micropipettes and perfused. Transepithelial potential difference (PD), short-circuit current (Isc), and barrier resistance (Rm) in distal bronchi, determined by cable analysis, were -3.0 +/- 0.4 mV, 50.7 +/- 5.9 microA/cm2, and 59.6 +/- 5.9 omega.cm2, respectively (means +/- SE). Bumetanide (10 microM), which blocks Cl- secretion through inhibition of Na(+)-K(+)-2Cl- cotransport, reduced Isc in distal bronchi by 30.0 +/- 5.5 microA/cm2 (59.0% of the total Isc). By comparison, a previous study of porcine distal airways [S.T. Ballard and A.E. Taylor, Am. J. Physiol. 267 (Lung Cell. Mol. Physiol. 11): L79-L84, 1994] determined that bumetamide-sensitive Isc in bronchioles was 2.6 +/- 1.4 microA/cm2 (only 9.0% of the total Isc). Submucosal gland duct openings to the luminal surface were identified microscopically and counted in representative fields. In eight bronchioles, 6.8 +/- 4.4 gland duct openings/cm2 of airway surface were observed, whereas seven distal bronchi contained 916.8 +/- 84.0 gland duct openings/cm2, over a 100-fold difference. These data suggest that a direct relationship may exist between the magnitude of active transepithelial Cl- secretion and the presence of submucosal glands in normal distal airways.