Functional characterization of malaria parasites deficient in the K(+) channel Kch2

缺乏K(+)通道Kch2的疟原虫的功能表征

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Abstract

K(+) channels are integral membrane proteins, which contribute to maintain vital parameters such as the cellular membrane potential and cell volume. Malaria parasites encode two K(+) channel homologues, Kch1 and Kch2, which are well-conserved among members of the Plasmodium genus. In the rodent malaria parasite P. berghei, the functional significance of K(+) channel homologue PbKch2 was studied using targeted gene knock-out. The knockout parasites were characterized in a mouse model in terms of growth-kinetics and infectivity in the mosquito vector. Furthermore, using a tracer-uptake technique with (86)Rb(+) as a K(+) congener, the K(+) transporting properties of the knockout parasites were assessed. RESULTS: Genetic disruption of Kch2 did not grossly affect the phenotype in terms of asexual replication and pathogenicity in a mouse model. In contrast to Kch1-null parasites, Kch2-null parasites were fully capable of forming oocysts in female Anopheles stephensi mosquitoes. (86)Rb(+) uptake in Kch2-deficient blood-stage P. berghei parasites (Kch2-null) did not differ from that of wild-type (WT) parasites. About two-thirds of the (86)Rb(+) uptake in WT and in Kch2-null parasites could be inhibited by K(+) channel blockers and could be inferred to the presence of functional Kch1 in Kch2 knockout parasites. Kch2 is therefore not required for transport of K(+) in P. berghei and is not essential to mosquito-stage sporogonic development of the parasite.

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