Perturbation of the pump-leak balance for Na+ and K+ in malaria-infected erythrocytes

Henry M. Staines, J. Clive Ellory, Kiaran Kirk*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    113 Citations (Scopus)

    Abstract

    In human erythrocytes infected with the mature form of the malaria parasite Plasmodium falciparum, the cytosolic concentration of Na+ is increased and that of K+ is decreased. In this study, the membrane transport changes underlying this perturbation were investigated using a combination of 86Rb+,43K+, and 22Na+ flux measurements and a semiquantitative hemolysis technique. From >15 h postinvasion, there appeared in the infected erythrocyte membrane new permeation pathways (NPP) that caused a significant increase in the basal ion permeability of the erythrocyte membrane and that were inhibited by furosemide (0.1 mM). The NPP showed the selectivity sequence Cs+ > Rb+ > K+ > Na+, with the K+-to-Na+ permeability ratio estimated as 2.3. From 18 to 36 h postinvasion, the activity of the erythrocyte Na+/K+ pump increased in response to increased cytosolic Na+ (a consequence of the increased leakage of Na+ via the NPP) but underwent a progressive decrease in the latter 12 h of the parasite's occupancy of the erythrocyte (36-48 h postinvasion). Incorporation of the measured ion transport rates into a mathematical model of the human erythrocyte indicates that the induction of the NPP, together with the impairment of the Na+/K+ pump, accounts for the altered Na+ and K+ levels in the host cell cytosol, as well as predicting an initial decrease, followed by a lytic increase in the volume of the host erythrocyte.

    Original languageEnglish
    Pages (from-to)C1576-C1587
    JournalAmerican Journal of Physiology - Cell Physiology
    Volume280
    Issue number6 49-6
    DOIs
    Publication statusPublished - 2001

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