Three types of spontaneously active anionic channels in malaria-infected human red blood cells

Three types of spontaneously active anionic channels in malaria-infected human red blood cells
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DOI:
10.1016/j.bcmd.2006.01.005
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发表时间:
2006-03-01
影响因子:
2.3
通讯作者:
Thomas, SL
Thomas, SL
中科院分区:
医学4区
文献类型:
--
作者:
Bouyer, G;Egée, S;Thomas, SL

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红细胞(RBC)的电生理学研究,使用膜片钳技术,已经经历了复兴,最近发现了恶性疟原虫感染的人RBC的宿主质膜中的新通道活性(S.A. Desai等人,Nature 406,1001-1005,2000; S.M. Huber等人,EMBO J. 21(2002)22-30; S. Egee等人,542(2002)795-801)。这是因为发现疟疾感染的RBC由于诱导新的渗透途径(NPP)而改变了渗透性特征(H。Ginsburg,Novartis Foundation Symposium 226(1999)99-108; K. Kirk,Physiol.Rev.81(2001)495-537),其使用非电生理学技术被定义为具有阴离子通道的一般特征(即高阴离子渗透性、线性浓度依赖性、不能区分渗透溶质的立体异构体)。发现NPP的有效和特异性抑制剂是一个重要的治疗挑战,但仍有太多问题没有答案:NPP对应于单一途径还是多个途径?它们是寄生虫衍生的蛋白质吗?它们是上调或修饰的内源性静止红细胞蛋白吗?这篇文章关注的是在疟疾感染的人红细胞中表达的不同类型的阴离子通道的鉴定。这些不同类型的通道在感染的红细胞和它们的功能意义的存在的影响进行了讨论。(c)2006年爱思唯尔公司All rights reserved.
The electrophysiological study of red blood cells (RBCs), using the patch-clamp technique, has been going through a renaissance with the recent discovery of novel channel activity in the host plasma membrane of Plasmodium falciparum-infected human RBCs (S.A. Desai et at., Nature 406, 1001-1005, 2000; S.M. Huber et al., EMBO J. 21 (2002) 22-30; S. Egee et al., J. Physiol. 542 (2002) 795-801). This arose from the finding that malaria-infected RBCs have altered permeability characteristics due to the induction of new permeation pathways (NPPs) (H. Ginsburg, Novartis Foundation Symposium 226 (1999) 99-108; K. Kirk, Physiol. Rev. 81 (2001) 495-537), which are defined, using non-electrophysiological techniques, as having the general characteristics of anion channels (i.e. high anion permeability, linear concentration dependence, inability to distinguish between stereo-isomers of permeant solutes). Discovering potent and specific inhibitors of the NPPs is an important therapeutic challenge, but too many questions remain unanswered: do the NPPs correspond to a single path or multiple pathways? Are they parasite-derived proteins? Are they up-regulated or modified endogenous quiescent red blood cell proteins? This article concerns the identification of different types of anionic channels that are expressed in malaria-infected human RBCs. Implications regarding the presence of these different types of channels in infected RBCs and their functional significance are discussed. (c) 2006 Elsevier Inc. All rights reserved.