title: The Plasmodium falciparum-induced anion channel of human erythrocytes is an ATP-release pathway.
abstract: Infection with the malaria parasite Plasmodium falciparum induces osmolyte and anion channels in the host erythrocyte membrane involving ATP release and autocrine purinergic signaling. P. falciparum-parasitized but not unstimulated uninfected erythrocytes released ATP in a 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB; 7 microM)-sensitive and serum album (SA; 0.5% w/v)-stimulated manner. Since Plasmodium infection of human erythrocytes induces SA-dependent outwardly (OR) and SA-independent inwardly rectifying (IR) anion conductances, we tested whether the infection-induced OR channels directly generate an ATP release pathway. P. falciparum-parasitized erythrocytes were recorded in whole-cell mode with either Cl(-) or ATP as the only anion in the bath or pipette. In parasitized cells with predominant OR activity, replacement of bath NaCl by Na-ATP (NMDG-Cl pipette solution) shifted the current reversal potential (V (rev)) from -2 +/- 1 to +51 +/- 3 mV (n = 15). In cells with predominant IR activity, in contrast, the same maneuver induced a shift of V (rev) to significantly larger (p < or = 0.05, two-tailed t test) values (from -3 +/- 1 to +66 +/- 8 mV; n = 5) and an almost complete inhibition of outward current. The anion channel blocker NPPB reversibly decreased the ATP-generated OR currents from 1.1 +/- 0.1 nS to 0.2 +/- 0.05 nS and further shifted V (rev) to +87 +/- 7 mV (n = 12). The NPPB-sensitive fraction of the OR reversed at +48 +/- 4 mV suggesting a relative permeability of P (ATP)/P (Cl) approximately 0.01. Together, these data raise the possibility that the OR might be the electrophysiological correlate of an erythrocyte ATP release pathway.
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Canan
authors.initials: C
authors.lastname: Akkaya
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.forename: Diwakar
authors.initials: D
authors.lastname: Bobballa
authors.forename: Verena B
authors.initials: VB
authors.lastname: Brand
authors.forename: Hasan
authors.initials: H
authors.lastname: Mahmud
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000838:Anions / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009579:Nitrobenzoates / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000502:physiology*
chemical_list: D000838:Anions; D007473:Ion Channels; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000255:Adenosine Triphosphate