title: Prostaglandin E2 increases 7-pS Cl- channel density in the apical membrane of A6 distal nephron cells.
abstract: In A6 distal nephron cells, short-circuit current (Isc) was increased by basolateral exposure to prostaglandin E2 (PGE2; peak response at 1 microM). 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 PGE2 and 3.7-fold with longer (10-50 min) exposure to PGE2. The PGE2-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 PGE2-induced increase in the amiloride-insensitive Isc, and 2) 7-pS Cl- channel activation was mediated via an increase in channel density without substantial effects on channel kinetics.
authors.affiliation: Emory University School of Medicine, Department of Physiology, Atlanta, Georgia, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Kokko
authors.forename: P S
authors.initials: PS
authors.lastname: Matsumoto
authors.forename: Z R
authors.initials: ZR
authors.lastname: Zhang
authors.forename: B N
authors.initials: BN
authors.lastname: Ling
authors.forename: D C
authors.initials: DC
authors.lastname: Eaton
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism* / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D007425:Intracellular Membranes / Q000378:metabolism; D009399:Nephrons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D018118:Chloride Channels; D000584:Amiloride; D015232:Dinoprostone