Prostaglandin E-2 increases 7-pS Cl- channel density in the apical membrane of A6 distal nephron cells

In A6 distal nephron cells, short-circuit current (I-sc) was increased by basolateral exposure to prostaglandin E-2 (PGE(2); peak response at 1 mu M). The effect was only partially abolished by either apical amiloride, an Na+ channel blocker, or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), a Cl- channel blocker. In apical cell-attached patches, we observed a 7-pS Cl- channel with a linear current-voltage relationship, a reversal potential near resting membrane potential, and open probability >0.5. The channel was blocked by diphenylamine-2-carboxylate, glibenclamide, and NPPB but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The frequency of observed Cl- channel activity increased 7-fold with 10-min exposure to PGE(2) and 3.7-fold with longer (10-50 min) exposure to PGE(2). The PGE(2)-induced increase in Cl- channel activity was due primarily to an increase in the number of functional channels. The following conclusions were made: 1) activation of apical, 7-pS Cl- channels in A6 cells accounts for the PGE(2)-induced increase in the amiloride-insensitive I-sc, and 2) 7-pS Cl- channel activation was mediated via an increase in channel density without substantial effects on channel kinetics.