Anionic channels in malaria-infected human red blood cells

As the intraerythrocytic stage of the human malarial parasite, Plasmodium falciparum, matures, the plasma membrane of the host red blood cell (RBC) becomes increasingly permeable to a variety of physiologically relevant solutes via the induction of new permeation pathways (NPPs) (H. Ginsburg, Novartis Foundation Symposium 226, 99-108,1999; K. Kirk, Physiol. Rev. 81, 495-537, 2001). Although permeable to cationic and electroneutral solutes, transport studies have shown that the NPPs exhibit the general properties of anion channels and recent electrophysiological studies, using the patch-clamp technique, have demonstrated that anion channels are activated in the plasma membrane of the RBC following infection (S.A. Desai et al., Nature 406, 1001-1005, 2000; S.M. Huber et al., EMBO J. 21, 22-30,2002; S. Egee et al., J. Physiol. 542, 795-801, 2002). In this paper, we review the features of the anionic channels that we have observed in both uninfected and malaria-infected human RBCs, the data that suggest that the NPPs are endogenous to the RBC membrane, and present new evidence, which suggests that the mechanism of induction of the NPPs, used by the parasite, involves phosphorylation steps.