Calcium regulation in the intraerythrocytic malaria parasite Plasmodium falciparum

The regulation of intracellular Ca²⁺ in the intraerythrocytic form of the human malaria parasite, Plasmodium falciparum, was investigated using parasites 'isolated' from their host cells by saponin-permeabilisation of the erythrocyte membrane. The isolated parasites maintained tight control over their resting cytosolic Ca²⁺ concentration which ranged from ∼100 nM in the absence of extracellular Ca²⁺ to ∼700 nM in the presence of 1 mM extracellular Ca²⁺. The parasite has two functionally discrete intracellular Ca²⁺ stores. One is an 'endoplasmic reticulum (ER)-like' store, the other an 'acidic store'. The ER-like store was discharged by cyclopiazonic acid (CPA), an inhibitor of sarco/endoplasmic reticulum Ca²⁺-ATPases (SERCAs) of animal and plant cells, but not by thapsigargin (TG), a more specific inhibitor of SERCAs of animal cells. The acidic store was discharged by nigericin and by NH₄⁺. The amount of Ca²⁺ in the ER-like store increased with increasing extracellular Ca²⁺ concentration, whereas the amount of Ca²⁺ in the acidic store did not. Ca²⁺ released from the ER-like store by CPA was cleared from the parasite cytosol by uptake into the acidic store (over a range of extracellular Ca²⁺ concentrations), consistent with the acidic store serving as a Ca²⁺ reservoir within the intracellular parasite.