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 similar to 100 nM in the absence of extracellular Ca2+ to similar 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. (C) 2001 Elsevier Science B.V. All rights reserved.