An acid-loading chloride transport pathway in the intraerythrocytic malaria parasite, Plasmodium falciparum

Roselani I. Henry, Simon A. Cobbold, Richard J.W. Allen, Asif Khan, Rhys Hayward, Adele M. Lehane, Patrick G. Bray, Susan M. Howitt, Giancarlo A. Biagini, Kevin J. Saliba, Kiaran Kirk*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)


    The intraerythrocytic malaria parasite exerts tight control over its ionic composition. In this study, a combination of fluorescent ion indicators and 36Cl- flux measurements was used to investigate the transport of Cl- and the Cl--dependent transport of "H+-equivalents" in mature (trophozoite stage) parasites, isolated from their host erythrocytes. Removal of extracellular Cl-, resulting in an outward [Cl-] gradient, gave rise to a cytosolic alkalinization (i.e. a net efflux of H+-equivalents). This was reversed on restoration of extracellular Cl-. The flux of H +-equivalents was inhibited by 4,4′-diisothiocyanostilbene-2, 2′-disulfonic acid and, when measured in ATP-depleted parasites, showed a pronounced dependence on the pH of the parasite cytosol; the flux was low at cytosolic pH values < 7.2 but increased steeply with cytosolic pH at values > 7.2. 36Cl- influx measurements revealed the presence of a Cl- uptake mechanism with characteristics similar to those of the Cl--dependent H+-equivalent flux. The intracellular concentration of Cl- in the parasite was estimated to be ∼48 mM in situ. The data are consistent with the intraerythrocytic parasite having in its plasma membrane a 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid-sensitive transporter that, under physiological conditions, imports Cl - together with H+-equivalents, resulting in an intracellular Cl- concentration well above that which would occur if Cl- ions were distributed passively in accordance with the parasite's large, inwardly negative membrane potential.

    Original languageEnglish
    Pages (from-to)18615-18626
    Number of pages12
    JournalJournal of Biological Chemistry
    Issue number24
    Publication statusPublished - 11 Jun 2010


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