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Functional state of the plasma membrane Ca²⁺ pump in Plasmodium falciparum-infected human red blood cells

Teresa Tiffert, Henry M. Staines*, J. Clive Ellory* and Virgilio L. Lew

1. The active Ca²⁺ transport properties of malaria-infected, intact red blood cells are unknown. We report here the first direct measurements of Ca²⁺ pump activity in human red cells infected with Plasmodium falciparum, at the mature, late trophozoite stage.

2. Ca²⁺ pump activity was measured by the Co²⁺-exposure method adapted for use in low-K⁺ media, optimal for parasitised cells. This required a preliminary study in normal, uninfected red cells of the effects of cell volume, membrane potential and external Na⁺/K⁺ concentrations on Ca²⁺ pump performance.

3. Pump-mediated Ca²⁺ extrusion in normal red cells was only slightly lower in low-K⁺ media relative to high-K⁺ media despite the large differences in membrane potential predicted by the Lew-Bookchin red cell model. The effect was prevented by clotrimazole, an inhibitor of the Ca²⁺-sensitive K⁺ (K_Ca) channel, suggesting that it was due to minor cell dehydration.

4. The Ca²⁺-saturated Ca²⁺ extrusion rate through the Ca²⁺ pump (V_max) of parasitised red cells was marginally inhibited (2-27 %) relative to that of both uninfected red cells from the malaria-infected culture (cohorts), and uninfected red cells from the same donor kept under identical conditions (co-culture). Thus, Ca²⁺ pump function is largely conserved in parasitised cells up to the mature, late trophozoite stage.

5. A high proportion of the ionophore-induced Ca²⁺ load in parasitised red cells is taken up by cytoplasmic Ca²⁺ buffers within the parasite. Following pump-mediated Ca²⁺ removal from the host, there remained a large residual Ca²⁺ pool within the parasite which slowly leaked to the host cell, from which it was pumped out.

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