Electrophysiological properties of the Plasmodium Falciparum-induced cation conductance of human erythrocytes.
Intraerythrocyte survival of the malaria pathogen Plasmodium Falciparum depends on the induction of the new-permeability-pathways (NPPs) in the host cell membrane. NPPs are characterized as anion- and organic osmolyte-permeable channels which also exhibit a low but significant permeability for inorganic cations. To disclose the electrophyiologial properties of this infection-induced cation permeability whole-cell currents were recorded in Plasmodium Falciparum-infected human erythrocytes (pRBC) using bath and pipette solutions with low Cl(-) concentrations. The data disclose a nonselective cation conductance (G(CAT)) which activated upon removal of extracellular Cl(-). Upon activation, G(CAT) was 0.3 +/- 0.05 nS (n=16) in control RBC and 2.0 +/- 0.3 nS (n = 32) in pRBC indicating an induction of G(CAT) during the infection. G(CAT) of pRBC exibited a relative permselectivity for monovalent cations of Cs(+)ñK(+)>Na(+)>Li(+) (P(Na)/P(K) ñ 0.5) with a significant permeability for Ca(2+). G(CAT) of pRBC was inhibited by NPPs blockers (furosemide and NPPB) and cation channel blockers (amiloride, EIPA, GdCl(3)) with the highest sensitivity to EIPA (IC(50)-0.5 microM). Most importantly, the blocker sensitivities differed between the infection-induced anion conductances and G(CAT) suggesting that G(CAT) and the anion conductances represent different channel proteins which in concert build up the NPPs.
Duranton
Christophe
C
Department of Physiology, University of Tuebingen.
Huber
Stephan
S
Tanneur
Valérie
V
Lang
Karl
K
Brand
Verena
V
Sandu
Ciprian
C
Lang
Florian
F
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002412:Cations; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D018408:Patch-Clamp Techniques; D010963:Plasmodium falciparum / Q000502:physiology*
D015220:Calcium Channels; D002412:Cations; D000584:Amiloride; C039614:ethylisopropylamiloride