Effect of Ion Channel Inhibitors on the Cytopathogenicity of Entamoeba histolytica

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Abstract
Entamoeba histolytica (axenic strain HMI-IMSS), a cytolytic enteric pathogen, kills target Chinese hamster ovary cells in two discrete steps: (1) carbohydrate-specific adherence of amoebae to target cells, followed by (2) cytolysis of adherent target cells. Both steps require intact amoebic microfilament function. The effects of the fast Na' channel blocker tetrodotoxin and the slow Na-Ca” channel blockers verapamil (10−5 M) and bepridil (10−5 M) on amoebic killing were evaluated. Verapamil and bepridil both decreased amoebic killing (P < 0.001); tetrodotoxin had no effect. Bepridil, but not verapamil, inhibited amoebic adherence at 37 C (P < 0.001). Both verapamil and bepridil inhibited amoebic lysis of cells after adherence occurred (P < 0.001). Verapamil protected target cells from lysis by amoebae (P P < 0.001). These findings suggest that changes in transmembrane ion flux in both the amoeba and the target cell are involved in amoebic killing of target cells.