The Membrane Potential of the Intraerythrocytic Malaria Parasite Plasmodium falciparum*

The membrane potential (Δψ) of the mature asexual form of the human malaria parasite, Plasmodium falciparum, isolated from its host erythrocyte using a saponin permeabilization technique, was investigated using both the radiolabeled Δψ indicator tetraphenylphosphonium ([3H]TPP+) and the fluorescent Δψ indicator DiBAC4(3) (bis-oxonol). For isolated parasites suspended in a high Na+, low K+ solution, Δψ was estimated from the measured distribution of [3H]TPP+ to be –95 ± 2 mV. Δψ was reduced by the specific V-type H+ pump inhibitor bafilomycin A1, by the H+ ionophore CCCP, and by glucose deprivation. Acidification of the parasite cytosol (induced by the addition of lactate) resulted in a transient hyperpolarization, whereas a cytosolic alkalinization (induced by the addition of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{NH}_{4}^{+}\) \end{document}) resulted in a transient depolarization. A decrease in the extracellular pH resulted in a membrane depolarization, whereas an increase in the extracellular pH resulted in a membrane hyperpolarization. The parasite plasma membrane depolarized in response to an increase in the extracellular K+ concentration and hyperpolarized in response to a decrease in the extracellular K+ concentration and to the addition of the K+ channel blockers Ba2+ or Cs+ to the suspending medium. The data are consistent with Δψ of the intraerythrocytic P. falciparum trophozoite being due to the electrogenic extrusion of H+ via the V-type H+ pump at the parasite surface. The current associated with the efflux of H+ is countered, in part, by the influx of K+ via Ba2+- and Cs+-sensitive K+ channels in the parasite plasma membrane.