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

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 al., 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.