Duranton Christophe, Huber Stephan, Tanneur Valérie, Lang Karl, Brand Verena, Sandu Ciprian, Lang Florian
Department of Physiology, University of Tuebingen.
Cell Physiol Biochem. 2003;13(4):189-98. doi: 10.1159/000072421.
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.
疟原虫恶性疟原虫在红细胞内的存活依赖于宿主细胞膜上新通透性途径（NPPs）的诱导。NPPs的特征是阴离子和有机渗透溶质可通透的通道，对无机阳离子也表现出低但显著的通透性。为了揭示这种感染诱导的阳离子通透性的电生理特性，使用低Cl⁻浓度的浴液和吸管溶液，在感染恶性疟原虫的人红细胞（pRBC）中记录全细胞电流。数据揭示了一种非选择性阳离子电导（G(CAT)），它在去除细胞外Cl⁻后被激活。激活后，对照红细胞中的G(CAT)为0.3±0.05 nS（n = 16），pRBC中的为2.0±0.3 nS（n = 32），表明感染期间G(CAT)被诱导。pRBC的G(CAT)对单价阳离子Cs⁺＞K⁺＞Na⁺＞Li⁺表现出相对的通透选择性（P(Na)/P(K)≈0.5），对Ca²⁺有显著通透性。pRBC的G(CAT)被NPPs阻滞剂（呋塞米和NPPB）和阳离子通道阻滞剂（氨氯地平、EIPA、GdCl₃）抑制，对EIPA敏感性最高（IC₅₀ - 0.5 μM）。最重要的是，感染诱导的阴离子电导和G(CAT)之间的阻滞剂敏感性不同，这表明G(CAT)和阴离子电导代表不同的通道蛋白，它们共同构成了NPPs。
