A voltage-dependent channel involved in nutrient uptake by red blood cellsinfected with the malaria parasite

Growth of the malaria parasite in human red blood cells (RBCs) is accompani ed by an increased uptake of many solutes including anions(1), sugars(2), p urines(3), amino acids(4) and organic cations(5). Although the pharmacologi cal properties and selectivity of this uptake suggest that a chloride chann el is involved, the precise mechanism has not been identified. Moreover, th e location of this uptake in the infected RBC is unknown because tracer stu dies are complicated by possible uptake through fluid-phase pinocytosis(6) or membranous ducts(7). Here we have studied the permeability of infected R BCs using the whole-cell voltage-clamp method. With this method, uninfected RBCs had ohmic whole-cell conductances of less than 100 pS, consistent wit h their low tracer permeabilities(8). In contrast, trophozoite-infected RBC s exhibited voltage-dependent, non-saturating currents that were 150-fold l arger, predominantly carried by anions and abruptly abolished by channel bl ockers. Patch-clamp measurements and spectral analysis confirmed that a sma ll (<10 pS) ion channel on the infected RBC surface, present at about 1,000 copies per cell, is responsible for these currents. Because its pharmacolo gical properties and substrate selectivities match those seen with tracer s tudies, this channel accounts for the increased uptake of small solutes in infected RBCs. The surface location of this new channel and its permeabilit y to organic solutes needed for parasite growth indicate that it may have a primary role in a sequential diffusive pathway for parasite nutrient acqui sition.