Calcium regulation in the intraerythrocytic malaria parasite Plasmodium falciparum

• Published in: Molecular and biochemical parasitology Vol. 117; no. 2; pp. 121 - 128
• Main Authors: Alleva, Lisa M, Kirk, Kiaran
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2001
• Subjects: Acidocalcisome; Animals; Ca 2+ homeostasis; Calcium - metabolism; Culture Media; cyclopiazonic acid; Erythrocytes - parasitology; Homeostasis; Hydrogen-Ion Concentration; Indoles - pharmacology; Malaria; Malaria, Falciparum - parasitology; nigericin; Nigericin - pharmacology; Plasmodium; Plasmodium falciparum; Plasmodium falciparum - physiology; Quaternary Ammonium Compounds - pharmacology; thapsigargin; Thapsigargin - pharmacology; Ca 2+ homeostasis; Malaria; [Ca 2+] cyt, cytosolic Ca 2+ concentration; AM, acetoxymethyl ester; SERCA, sarco/endoplasmic reticulum Ca 2+-ATPase; Δ[Ca 2+] cyt, increase in cytosolic Ca 2+ concentration; Acidocalcisome; CPA, cyclopiazonic acid; HEPES, N-2-hydroxyethyl piperazine- N′-2-ethanesulfonic acid; Plasmodium; TG, thapsigargin; BCECF, 2′7′-bis(2-carboxyethyl)-5-(and-6)-carboxyfluorescein; pH cyt, cytosolic pH; HTC, rat hepatoma cells; [Ca 2+] out, extracellular Ca 2+ concentration; ER, endoplasmic reticulum
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/S0166-6851(01)00338-3

The regulation of intracellular Ca 2+ 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 Ca 2+ concentration which ranged from ∼100 nM in the absence of extracellular Ca 2+ to ∼700 nM in the presence of 1 mM extracellular Ca 2+. The parasite has two functionally discrete intracellular Ca 2+ 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 Ca 2+-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 NH 4 +. The amount of Ca 2+ in the ER-like store increased with increasing extracellular Ca 2+ concentration, whereas the amount of Ca 2+ in the acidic store did not. Ca 2+ 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 Ca 2+ concentrations), consistent with the acidic store serving as a Ca 2+ reservoir within the intracellular parasite.