Acidifying defect induced by amphotericin B: comparison of bicarbonate and hydrogen ion permeabilities

Abstract

The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence of imposed bicarbonate ion gradients, comparable to those occurring in vivo. With mucosal (M) pH lowered to the point of zero net hydrogen ion secretion, the transepithelial flow of bicarbonate ions (J(HCO3)) from serosa (S) to M was 0.91 ± 0.06 μmole/hr in response to a 20 mM HCO3- gradient. After AMB addition to M, back diffusion of hydrogen ions from M to S (-J(H)) increased from zero to 0.36 ± 0.05 μmole/hr, whereas bicarbonate ion transport from S to M (J(HCO3)) failed to increase (0.91 ± 0.06 before and 0.82 ± 0.09 μmole/hr after AMB). In contrast to M addition, S addition of AMB had no effect on either - J(H) or J(HCO3). The defect in urinary acidification induced by AMB is characterized by a large increase in the permeability for hydrogen ions rather than that for bicarbonate ions and depends on direct exposure of the luminal cell membrane to AMB. The permeability increase is cation selective, not only for hydrogen ions but also, as shown previously, for potassium ions, and to lesser extent, for sodium ions. The results are consistent with the formation by AMB of aqueous half pores in the luminal membrane. Although the passive permeabilities for bicarbonate and chloride ions are not affected primarily, they may increase after prolonged exposure, probably as a result of paracellular leaks that are not specific for AMB.