The malaria parasite has a complex life cycle with intra- and extra- cellular stages, during which it encounters a variety of environments, many harsh. At each stage, the parasite must have specialized adaptations for acquisition of nutrients, removal of soluble metabolic wastes, and maintenance of ionic gradients. Membrane transport proteins likely mediate all of these. The patch clamp method has been used to identify two of these ion channels for the erythrocytic stage. First, there is a small (5 pS) ion channel on the surface of red cells infected with mature parasites. This channel is primarily permeable to anions and small nutrients, inhibited by several channel blockers (albeit poorly), and is present at ~2000 copies/cell. Second, there is a separate large (150 pS) nonselective channel on the membrane surrounding the intracellular parasite. This second channel has a pore size of 23 angstroms and functions as a molecular sieve, providing the parasite access to soluble nutrients in red cell cytosol. We are working to further characterize these channels and clone their genes. Because of their important roles in the parasite?s adaptation to the red cell, they may be ideal targets for new channel blockers or vaccines.Other membrane transporters of the parasite will also be identified by using the growing malaria genome database and heterologous expression in oocytes. - Malaria, ion channels, nutrients, Plasmodium falciparum, transporters, patch clamp
| Bezrukov, S M; Winterhalter, M (2000) Examining noise sources at the single-molecule level: 1/f noise of an open maltoporin channel. Phys Rev Lett 85:202-5 |
| Rostovtseva, T K; Liu, T T; Colombini, M et al. (2000) Positive cooperativity without domains or subunits in a monomeric membrane channel. Proc Natl Acad Sci U S A 97:7819-22 |
| Bezrukov, S M; Kullman, L; Winterhalter, M (2000) Probing sugar translocation through maltoporin at the single channel level. FEBS Lett 476:224-8 |
| Desai, S A; Bezrukov, S M; Zimmerberg, J (2000) A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 406:1001-5 |
