Electrophysiological studies of malaria parasite-infected erythrocytes: current status

Abstract

The altered permeability characteristics of erythrocytes infected with malaria parasites have been a source of interest for over 30 years. Recent electrophysiological studies have provided strong evidence that these changes reflect transmembrane transport through ion channels in the host erythrocyte plasma membrane. However, conflicting results and differing interpretations of the data have led to confusion in this field. In an effort to unravel these issues, the groups involved recently came together for a week of discussion and experimentation. In this article, the various models for altered transport are reviewed, together with the areas of consensus in the field and those that require a better understanding.

Fig. 1

Current consensus within the field regarding the altered permeability of Plasmodium falciparum-infected human erythrocytes.

Fig. 2

Patch-clamp configurations used to characterise channel activity in Plasmodium falciparum-infected human erythrocytes. (A) The cell-attached configuration. (B) The inside-out configuration. (C) The whole-cell configuration. Note that the erythrocytes depicted in the figure are not infected.

Fig. 3

Models for the altered permeability of Plasmodium falciparum-infected human erythrocytes. Depicted are the parasite plasma membrane (PPM), a second membrane that surrounds the parasite, termed the parasitophorous vacuole membrane (PVM), and the erythrocyte plasma membrane (EPM). Channels/pores are represented by cylinders in the appropriate membrane, where red channels/pores are proposed to be important for parasite survival, the white channels/pores are unlikely to be essential for the parasite, and in the case of the green channels/pores there is no evidence one way or the other. PSAC, plasmodial surface anion channel; CUC-2, chloride channel family member 2; IRC, inward rectifying channel; ORCC, outward rectifying conductance channel; NSCC, nonspecific cation channel; ICAC, intermediate conductance anion channel; SCAC, small conductance anion channel; ORLCAC, outwardly rectifying large conductance anion channel; CFTR, cystic fibrosis transmembrane regulator; IRCAC, inwardly rectifying conductance anion channel.