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1: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6398-402. Epub 2008 Apr 23.
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Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption.

Ellekvist P, Maciel J, Mlambo G, Ricke CH, Colding H, Klaerke DA, Kumar N.

Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Regulated K(+) transport across the plasma membrane is of vital importance for the survival of most cells. Two K(+) channels have been identified in the Plasmodium falciparum genome; however, their functional significance during parasite life cycle in the vertebrate host and during transmission through the mosquito vector remains unknown. We hypothesize that these two K(+) channels mediate the transport of K(+) in the parasites, and thus are important for parasite survival. To test this hypothesis, we identified the orthologue of one of the P. falciparum K(+) channels, PfKch1, in the rodent malaria parasite P. berghei (PbKch1) and examined the biological role by performing a targeted disruption of the gene encoding PbKch1. The deduced amino acid sequence of the six transmembrane domains of PfKch1 and PbKch1 share 82% identity, and in particular the pore regions are completely identical. The PbKch1-null parasites were viable despite a marked reduction in the uptake of the K(+) congener (86)Rb(+), and mice infected with PbKch1-null parasites survived slightly longer than mice infected with WT parasites. However, the most striking feature of the phenotype was the virtually complete inhibition of the development of PbKch1-null parasites in Anopheles stephensi mosquitoes. In conclusion, these studies demonstrate that PbKch1 contributes to the transport of K(+) in P. berghei parasites and supports the growth of the parasites, in particular the development of oocysts in the mosquito midgut. K(+) channels therefore may constitute a potential antimalarial drug target.

Publication Types:
PMID: 18434537 [PubMed - indexed for MEDLINE]

PMCID: PMC2359770