1887

Abstract

Summary: Trifluoperazine (TFP), the antipsychotic drug, induces substantial K efflux, membrane hyperpolarization and inhibition of H-ATPase in the yeast . Investigations on the mechanism of these effects revealed two different processes observed at different incubation conditions. At an acidic pH of 4.5 and an alkalinepH of 7.5, K efflux was accompanied by substantial proton influx which led to intracellular acidification and dissipation of Δ formed by cation efflux. The results indicated nonspecific changes in membrane permeability. Similar results were also observed when cells were incubated at pH 5.5–6.0 with higher concentrations of TFP (above 75 μm). On the other hand, low concentrations of TFP (30–50 μm) at pH 5.5–6.0 caused marked membrane hyperpolarization and K efflux unaccompanied by the efflux of other cations and by H influx. Our experiments indicate that under these conditions K efflux was an active process. (1) K efflux proceeded only in the presence of a metabolic substrate and was inhibited by metabolic inhibitors. (2) When 0.3–0.9 m-KCl was present in the medium at pH 6.0, the concentration of K within the cells (measured at the end of the incubation with TFP) was much lower than the theoretical concentration of if the distribution of K between medium and cell water was at equilibrium (at zero electrochemical gradient). (3) Valinomycin decreased the net K efflux and decreased the membrane hyperpolarization induced by TFP, probably by increasing the flux of K into the cells along its electrochemical gradient. (4) Conditions which led to active K efflux also led to a marked decrease in cellular ATP level. The results indicate that under a specific set of conditions TFP induces translocation of K against its electrochemical gradient.

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1985-10-01
2021-05-14
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