Is potassium toxic for schizonts?

Submitted by Irene Teis on November 10, 2014 – 13:18

On invading an uninfected human erythrocyte Plasmodium falciparum enters a low sodium, high potassium environment. It establishes new permeability pathways which allow the influx of sodium and efflux of potassium until reaching levels approaching those in the extraerythrocytic plasma., or eventually higher, leading to swelling and explosion of the erythrocyte. This flow is accelerated in late stages of schizont developpement (K Waller et al., Malaria Journal, 2008, 7 :19).

Cytoplasmic calcium is essential for malaria parasite egress from infected erythrocytes. A steady increase is found to preceed this egress (S Glushakova et al., Malaria Journal, 2013 12 :41). In Toxoplasma gondii it has been obsserved that the reduction in the host cell potassium causes an increase in cytoplasmic calcium.

As long as the host cells are healthy enough to maintain their normal cytosolic ion composition, they provide a suitable environment for parasite growth and the parasite will remain in the cell. If the resources of the host cell become exhausted due to the metabolic burden, a decrease in cytoplasmic potassium is noticed and this signal triggers the egress because the host cell can no longer support the replication and survival of the parasite (R Moudyet al., J Biol Chem. 2001, 276,41492-501).

A more recent in vitro study confirms most of these findings (A Pillai et al., Mol Microbiol 2013, 88, 20-34). The standard medium used for Plasmodium falciparum culture is human serum. It fulfills the requirement that the extracellular sodium concentration be high because the entry of sodium into infected cells is passive. When sodium is replaced by lithium or potasssium the parasite growth is interrupted. This may reflect on an indirect toxic effect of high potassium concentrations. This indirect toxicity might be related to the fact that potasium has a higher PSAC (plasmodium surface anion channel) permeability than sodium leading to osmotic lysis of infected cells. Potassium enrichment of the plasma leads to osmotical shrinkage of the infected erythrocyte, increased viscosity in the host cell cytoplasm and hemoglobin gelation. The supply of potassium acts like an antimalarial. The authors of this research work demonstrated that potassium really was an inhibitor of parasite growth, by adding sucrose to the parasite cultures. Sucrose acts as an impermeant of the PSAC channels and blocks the entry of extracellular potassium into the cytosol.

The precise contribution of potassium in plasmodium merozoite maturation and invasion should be reevaluated in light of these studies.The potassium channels in apicomplexan parasites like Plasmodium, Toxoplasma, Paramecium become novel targets for anti-parasitic drugs.

Many molecules present in Artemisia plants have an effect on erythrocyte cell membrane structure, permeability and cationic channels : phytosterols (K Hac-Wydro, Chem Phys Lipids 2010, 163, 689-97), steroids ( ML Lopez et al., Mem Instit Oswaldo Cruz, 104, 683-688, 2009), saponin (R Bissinger et al., Int J Hematol 2014, 100, 51-9), scopoletin (EJ Oliveira Planta Med 2001, 67, 605-8.

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