title: A novel pathway for Ca++ entry into Plasmodium falciparum-infected blood cells.
abstract: Growth of the human malaria parasite, Plasmodium falciparum, within the red blood cell (RBC) requires external Ca++ and is associated with a markedly elevated intracellular Ca++ concentration, [Ca++]i. We used 45Ca++ flux studies and patch clamp recordings to examine the mechanisms responsible for this increased [Ca++]i. The 45Ca++ flux studies indicated that net Ca++ entry into parasitized RBCs (PRBCs) is 18 times faster than into unparasitized ATPase that keeps the [Ca++]i of unparasitized RBCs exceedingly low. Acceleration of the preexisting Ca++ entry, ATPase that keeps the [Ca++] of unparasitized RBCs exceedingly low. Acceleration of the preexisting Ca++ entry, mediated by a divalent cation carrier, also cannot explain Ca++ accumulation in PRBCs: there are fundamental differences in substrate preference and in the effects of external Ca++ on 45Ca++ efflux between unparasitized RBCs and PRBCs. Patch clamp of intact PRBC surface membranes revealed rare unitary channel openings not observed on unparasitized RBCs. With 80 mM of CaCl2 in the patch pipette, this channel carried inward current, suggesting Ca++ entry at a rate comparable with the observed 45Ca++ flux. These data indicate that the malaria parasite induces a novel pathway in the host RBC membrane for Ca++ entry and suggest that this pathway is a Ca++-permeable channel.
authors.affiliation: Department of Cell Biology, Washington University, St. Louis, Missouri, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Desai
authors.forename: E W
authors.initials: EW
authors.lastname: McCleskey
authors.forename: P H
authors.initials: PH
authors.lastname: Schlesinger
authors.forename: D J
authors.initials: DJ
authors.lastname: Krogstad
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000469:parasitology; D010963:Plasmodium falciparum; D013379:Substrate Specificity
chemical_list: D015220:Calcium Channels; D000252:Calcium-Transporting ATPases; D002118:Calcium