Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption

Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6398-402. doi: 10.1073/pnas.0802384105. Epub 2008 Apr 23.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anopheles / parasitology
  • Gene Targeting*
  • Kinetics
  • Life Cycle Stages
  • Malaria / parasitology
  • Malaria / transmission*
  • Mice
  • Molecular Sequence Data
  • Parasites / genetics
  • Parasites / growth & development
  • Parasites / pathogenicity
  • Phenotype
  • Plasmodium berghei / genetics*
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / pathogenicity
  • Plasmodium falciparum
  • Potassium / metabolism
  • Potassium Channels / chemistry
  • Potassium Channels / genetics*
  • Rubidium / metabolism
  • Sequence Analysis, Protein
  • Sequence Homology, Amino Acid
  • Virulence


  • Potassium Channels
  • Rubidium
  • Potassium

Associated data

  • GENBANK/XP676033