AJP - Lung Cellular and Molecular Physiology, Vol 265, Issue 4 323-L329, Copyright © 1993 by American Physiological Society

ARTICLES

G protein-regulated large-conductance chloride channels in freshly isolated fetal type II alveolar epithelial cells

P. J. Kemp, G. G. MacGregor and R. E. Olver
Department of Child Health, Ninewells Hospital and Medical School, University of Dundee, United Kingdom.

Using the patch-clamp technique, we have recorded single channels in cell-attached and inside-out excised patches from the plasma membrane of type II alveolar epithelial cells freshly isolated from fetal guinea pig lung by elastase digestion and differential filtration. In cell-free patches the channels were highly selective for Cl- (PCl:Pcat = 9:1), had a large unitary conductance (375 pS +/- 23 pS), and current reversal of 0 mV in either symmetrical Na(+)-rich solutions or when the inner membrane leaflet was bathed in a K(+)-rich solution. The large-conductance Cl- channel exhibited little or no voltage inactivation at positive potentials, remained open for a significant amount of time at potentials negative to -40 mV, and was blocked at all potentials by 0.1 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. Channel activity was independent of intracellular calcium concentration. Bath addition of the nonmetabolizable analogue of GTP, GTP gamma S (0.1 mM), caused a voltage-dependent inhibition of channel activity [open probability (Po) plot was shifted by at least +25 mV]. Smaller channels (25 +/- 3 pS) were recorded in the cell-attached configuration with a current-voltage (I-V) relationship which was compatible with a Cl- conductance. On excision, the patches previously containing small-conductance channels exhibited only large-conductance Cl- channel behavior. These large-conductance, G protein-regulatable Cl- channels may provide a route for alveolar cell Cl- exit and as such may be an integral part of the mechanism responsible for secretion of fetal lung fluid.

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