Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
J Membr Biol. 2012 Dec;245(12):797-805. doi: 10.1007/s00232-012-9482-y. Epub 2012 Jul 27.
Survival of the malaria pathogen Plasmodium falciparum in host erythrocytes requires the opening of new permeability pathways (NPPs) in the host cell membrane, accomplishing entry of nutrients, exit of metabolic waste products such as lactate and movement of inorganic ions such as Cl⁻, Na⁺ and Ca²⁺. The molecular identity of NPPs has remained largely elusive but presumably involves several channels, which partially can be activated by oxidative stress in uninfected erythrocytes. One NPP candidate is aquaporin 9 (AQP9), a glycerol-permeable water channel expressed in erythrocytes. Gene-targeted mice lacking functional AQP9 (aqp⁻/⁻) survive infection with the malaria pathogen Plasmodium berghei better than their wild-type littermates (aqp9⁺/⁺). In the present study whole-cell patch-clamp recordings were performed to explore whether ion channel activity is different in erythrocytes from aqp⁻/⁻ and aqp9⁺/⁺ mice. As a result, the cation conductance (K⁺ > Na⁺ > Ca²⁺ ≫ NMDG⁺) was significantly lower in erythrocytes from aqp⁻/⁻ than in erythrocytes from aqp9⁺/⁺ mice. Oxidative stress by exposure for 15-30 min to 1 mM H₂O₂ or 1 mM tert-butyl-hydroperoxide enhanced the cation conductance and increased cytosolic Ca²⁺ concentration, effects significantly less pronounced in erythrocytes from aqp⁻/⁻ than in erythrocytes from aqp9⁺/⁺ mice. In conclusion, lack of AQP9 decreases the cation conductance of erythrocytes, an effect that possibly participates in the altered susceptibility of AQP9-deficient mice to infection with P. berghei.
疟原虫恶性疟原虫在宿主红细胞中的存活需要在宿主细胞膜上打开新的通透性途径（NPPs），完成营养物质的进入、代谢废物如乳酸的排出以及无机离子如 Cl⁻、Na⁺和 Ca²⁺的移动。NPPs 的分子特征在很大程度上仍然难以捉摸，但推测涉及几种通道，这些通道在未感染的红细胞中部分可以被氧化应激激活。NPP 的一个候选物是水通道蛋白 9（AQP9），一种在红细胞中表达的甘油通透性水通道。缺乏功能性 AQP9（aqp⁻/⁻）的基因靶向小鼠比其野生型同窝仔鼠（aqp9⁺/⁺）更好地存活感染疟原虫 Plasmodium berghei 的感染。在本研究中，进行了全细胞膜片钳记录，以探讨 aqp⁻/⁻和 aqp9⁺/⁺小鼠的红细胞中离子通道活性是否不同。结果表明，aqp⁻/⁻小鼠的红细胞阳离子电导（K⁺ > Na⁺ > Ca²⁺ ≫ NMDG⁺）明显低于 aqp9⁺/⁺小鼠的红细胞。通过暴露于 1 mM H₂O₂或 1 mM tert-butyl-hydroperoxide 15-30 分钟诱导的氧化应激增强了阳离子电导并增加了细胞内 Ca²⁺浓度，在 aqp⁻/⁻小鼠的红细胞中，这些效应明显小于 aqp9⁺/⁺小鼠的红细胞。总之，缺乏 AQP9 降低了红细胞的阳离子电导，这种效应可能参与了 AQP9 缺陷小鼠对 P. berghei 感染的易感性改变。
