New Permeation Pathways

Abstract

The Red blood cell (RBC) membrane is naturally endowed with a variety of membrane transporters, mainly geared to optimize the respiratory function and to maintain cell homeostasis at minimal metabolic cost. Therefore, to survive within a red blood cell, the malaria parasite must alter the permeability of the host’s plasma membrane by up-regulation of existing carriers or by creation of new permeation pathways (NPP).These pathways, indispensable for parasite growth, could be possible antimalarial targets for selective inhibition, as well as routes for drug delivery. Electrophysiological techniques, such as the patch clamp, are ideal for the study of channels that are permeable to charged solutes, even though the NPP are also used for transport of electroneutral and organic osmolytes in malaria infected RBCs. Red blood cells have proven to be extremely useful as a model system to study the different membrane transport pathways, and there is a plethora of publications aimed at a detailed description of pumps, cotransporters, and specific carriers in the red blood cell membrane. In the cell-attached and excised configurations, Plasmodium falciparum-infected RBCs show a very different pattern of channel activity from uninfected cells. It has been suggested that NPP could be used as therapeutic targets. However, the exact nature of the NPP remains to be resolved; part of the present confusion, due to discrepant results, comes from the lack of background information on the channels present in noninfected red blood cell membranes.