Permeability properties of cell membranes and tight junctions of normal and cystic fibrosis sweat ducts.

Abstract

The transepithelial permeability properties to Na, K, and Cl in microperfused segments of human eccrine sweat ducts from normal (N) subjects and patients with cystic fibrosis (CF) were examined. Amiloride administered on the luminal surface caused the transepithelial potential (Vt) of normal ducts to depolarize to 0 mV, but in the absence of Cl in the medium or in CF ducts, amiloride caused the Vt to significantly reverse electrical polarity from lumen negative to lumen positive with respect to the serosal bath. The Vt responses to changes in Na concentration in the lumen and K concentration in the bath were similar in CF and N ducts and showed that the basolateral membrane of the duct is K permeable and the apical membrane (in the absence of an anion shunt) is an almost ideal Na electrode. The Vt of N ducts was insensitive to 10-fold changes in luminal K and contraluminal Na solution concentrations. These responses show that in normal ducts, the apical membrane and tight junctions are relatively impermeable to K, and the basal membrane and tight junctions are relatively impermeable to Na. The Vt was highly sensitive to Cl- changes on either surface before or after ouabain inhibition in N ducts, but in every case were insensitive to Cl- changes in CF ducts. By comparison to control ducts the cation selective properties of the CF duct are probably normal, but both cell membranes as well as the tight junctions of the CF duct are relatively impermeable to Cl. The present data are inconclusive as to whether the route of Cl movement across the N duct epithelium is trans- or paracellular.