AJP - Cell Physiology, Vol 259, Issue 2 C295-C301, Copyright © 1990 by American Physiological Society
Apical membrane Cl- channels in airway epithelia: anion selectivity and effect of an inhibitor
M. Li, J. D. McCann and M. J. Welsh
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Previous work has investigated the anion selectivity of transepithelial Cl-
secretion by airway epithelia and its inhibition by the Cl(-)-channel
blocker 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB). Here we report the
anion selectivity of the apical membrane and of the outwardly rectifying
Cl- channel and the effect of NPPB on the Cl- channel. The anion
selectivity sequence of the apical membrane determined with conventional
microelectrodes in the native epithelium was SCN- greater than I- greater
than Br- greater than NO3- approximately Cl- much greater than SO(4)2-
approximately gluconate-. This contrasts with the observation that Cl- and
Br- support transepithelial secretion but that I- does not. Thus the anion
selectivity of transepithelial transport is determined by the basolateral
membrane Cl- entry step. The anion selectivity of the outwardly rectifying
Cl- channel studied in excised patches was the same as that of the apical
membrane. We also found that NPPB reversibly blocked the outwardly
rectifying Cl- channel from both the internal and external surfaces of the
patch. NPPB, 10 microM, completely blocked the channel; lower
concentrations caused a decrease in the probability of finding the channel
in the open state. NPPB also caused the appearance of a subconductance
state of the channel, an occurrence which is rarely observed in the absence
of NPPB. These data provide further support for the conclusion that the
outwardly rectifying Cl- channel is responsible for Cl- exit from the cell
across the apical membrane.
