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

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 (86)Rb(+), (43)K(+), and (22)Na(+) 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.

Plasmodium falciparum-activated Chloride Channels Are Defective in Erythrocytes from Cystic Fibrosis Patients

“…There was no difference in amplitude of the inwardly rectifying chloride channel compared with trophozoite-infected cells (Fig. 4D), implying that full activation of the channel is already achieved at an early stage of infection, long before activation of the new permeation pathway (n ϭ 4) (22).…”

New Insight into the Mechanism of Accumulation and Intraerythrocytic Compartmentation of Albitiazolium, a New Type of Antimalarial

“…While the recently described albitiazolium entry via NPP (18) likely explains its specific tropism for IRBC, these pore-like systems do not mediate concentrative processes (44). Albitiazolium accumulation requires intracellular binding sites or active transport in parasite-specific compartments, or a combination of both.…”

Na+/K+ATPase Activity in Sheep with Natural Babesiosis

“…Merckx et al (2009) also report that in order to survive within erythrocytes, parasites alter the permeability of the host plasma membrane, either by upregulating existing transporters, or by creating NPPs. Staines et al (2001) found that Na…”