A nutrient-permeable channel on the intraerythrocytic malaria parasite

Abstract

During its 48-hour cycle inside the red blood cell, the human malaria parasite, Plasmodium falciparum, increases its volume 25-fold and divides asexually. This rapid growth demands large amounts of nutrients, a problem exacerbated by the lower metabolic rate and relative ionic impermeability of the host red blood cell. Direct passage of small nutrients across the two membranes that separate the parasite from the erythrocyte cytosol may be important for parasite development and has been demonstrated for radiolabelled glucose, amino acids, and purine nucleosides. Flux studies on plasmodia are limited, however, to suspensions of erythrocyte-free parasites and so cannot be used to examine the individual transport properties of the two membranes involved. Here we use the cell-attached patch clamp method to overcome this limitation. After removing the intervening red blood cell membrane and forming gigaohm seals on the small (3-5 microns) parasite, we studied transport across the parasitophorous vacuole membrane (PVM), the outer of the two membranes that separate the parasite from the erythrocyte cytosol. A 140-pS channel which is permeable to both cations and anions was identified on the PVM. This channel is present at high density, is open more than 98 per cent of the time at the resting potential of the PVM, and is permeable to lysine and glucuronate. The channel can readily transport amino acids and monosaccharides across the PVM and may be essential for fulfilling the parasite's metabolic demands.