Membrane effects of chloride substitutes in guinea pig gallbladder epithelial cells.
Differences in the responses of guinea pig gallbladder epithelial cells to replacement of luminal Cl- with either isethionate (I), gluconate (G), sulfate (S), or cyclamate (C) were investigated in vitro using intracellular microelectrode techniques. In prostaglandin E1 (PGE1)-treated tissues (10(-6) M, serosal side), where electrodiffusive apical membrane Cl- permeability (PCla) is high, replacement of luminal Cl- caused transient membrane depolarizations of similar magnitudes but different times to peak (C greater than G = S greater than I). The subsequent shifts in membrane voltages were, at steady state, straight correlated with the concomitant increases in apparent ratio of apical to basolateral membrane resistances (Ra/Rb). Increases followed the rank order I greater than G = S greater than C, which was also found to be the case in the peak membrane hyperpolarizations on restoring luminal Cl-. Under control conditions (no PGE1, low PCla), three of the substitutes caused a slow hyperpolarization, C greater than G = S, whereas an I-for-Cl- substitution evoked a transient depolarization and a drop in Ra/Rb. Under both control and PGE1 conditions, a transient depolarization followed luminal I-for-C substitution. Our results are best explained by a stimulatory effect of I (and, less marked, G and S) on PCla. Intrinsic effects of cyclamate are not ruled out; however, among the substitutes examined, it is the most inert.
Wehner
F
F
Institut für Pharmakologie der Medizinischen Fakultät, Rheinisch-Westfälische, Technische Hochschule Aachen, Federal Republic of Germany.
Sigrist
G
G
Petersen
K U
KU
D000818:Animals; D000838:Anions; D002413:Cations, Divalent; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology*; D003494:Cyclamates / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005704:Gallbladder / Q000502:physiology*; D005942:Gluconates / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007513:Isethionic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D013431:Sulfates / Q000494:pharmacology
D000838:Anions; D002413:Cations, Divalent; D002712:Chlorides; D003494:Cyclamates; D005942:Gluconates; D013431:Sulfates; D007513:Isethionic Acid