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

Nature volume 406, pages 1001–1005 (2000)Cite this article

Abstract

Growth of the malaria parasite in human red blood cells (RBCs) is accompanied by an increased uptake of many solutes including anions1, sugars2, purines3, amino acids4 and organic cations5. Although the pharmacological properties and selectivity of this uptake suggest that a chloride channel is involved, the precise mechanism has not been identified. Moreover, the location of this uptake in the infected RBC is unknown because tracer studies are complicated by possible uptake through fluid-phase pinocytosis6 or membranous ducts7. Here we have studied the permeability of infected RBCs using the whole-cell voltage-clamp method. With this method, uninfected RBCs had ohmic whole-cell conductances of less than 100 pS, consistent with their low tracer permeabilities8. In contrast, trophozoite-infected RBCs exhibited voltage-dependent, non-saturating currents that were 150-fold larger, predominantly carried by anions and abruptly abolished by channel blockers. Patch-clamp measurements and spectral analysis confirmed that a small (< 10 pS) ion channel on the infected RBC surface, present at about 1,000 copies per cell, is responsible for these currents. Because its pharmacological properties and substrate selectivities match those seen with tracer studies, this channel accounts for the increased uptake of small solutes in infected RBCs. The surface location of this new channel and its permeability to organic solutes needed for parasite growth indicate that it may have a primary role in a sequential diffusive pathway for parasite nutrient acquisition.

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Figure 1: Whole-cell recordings.
Figure 2: On-cell currents on trophozoite-infected RBCs.
Figure 3: Power spectras of whole-cell (top and middle traces) and single-channel (bottom trace) currents.
Figure 4: Sequential route of nutrient acquisition.

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Acknowledgements

We thank L. Miller for steady help and advice, and S. Brazer, F. Cohen, A. Sher and T. Wellems for reviewing the manuscript.

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Authors and Affiliations

  1. The Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases,

    Sanjay A. Desai

  2. The Laboratory of Physical and Structural Biology,

    Sergey M. Bezrukov

  3. The Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Development, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Sanjay A. Desai & Joshua Zimmerberg

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Desai, S., Bezrukov, S. & Zimmerberg, J. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 406, 1001–1005 (2000). https://doi.org/10.1038/35023000

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