Mechanisms of the mucosa-negative transepithelial potential produced by amphotericin B in gallbladder epithelium.

Exposure of the apical (luminal) surface of gallbladder epithelium to the polyene antibiotic amphotericin B produces a mucosa-negative change of the transepithelial potential. The mechanism of this effect has been studied by both electrophysiologic techniques and tracer flux measurements. The main effect of amphotericin B appears to be an increase in the permeability of the apical membrane to small monovalent cations. During exposure to Na-Cl-Ringer's, this results in cell depolarization and in K loss and Na uptake by the cells. The loss of apical membrane K selectivity appears to account for most of the change in the transepithelial potential. Accumulation of K in the mucosal un-stirred layers can contribute to this change as well. The evidence for stimulation of an electrogenic basolateral Na pump (by the net Na entry caused by amphotericin B) is not conclusive due to a) indirect effects of the polyene antibiotic on the resistance of basolateral membrane, b) lack of reduction of the amphotericin B-dependent change of transepithelial potential when the pump is inhibited, and c) lack of effect of NaCl addition on basolateral membrane potential in tissues preincubated in high K-media and exposed to amphotericin B on the luminal side.