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The Plasmodium falciparum-induced anion channel of human erythrocytes is an ATP-release pathway

  • Ion Channels, Receptors and Transporters
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Abstract

Infection with the malaria parasite Plasmodium falciparum induces osmolyte and anion channels in the host erythrocyte membrane involving ATP release and autocrine purinergic signaling. P. falciparum-parasitized but not unstimulated uninfected erythrocytes released ATP in a 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB; 7 µM)-sensitive and serum album (SA; 0.5% w/v)-stimulated manner. Since Plasmodium infection of human erythrocytes induces SA-dependent outwardly (OR) and SA-independent inwardly rectifying (IR) anion conductances, we tested whether the infection-induced OR channels directly generate an ATP release pathway. P. falciparum-parasitized erythrocytes were recorded in whole-cell mode with either Cl− or ATP as the only anion in the bath or pipette. In parasitized cells with predominant OR activity, replacement of bath NaCl by Na–ATP (NMDG–Cl pipette solution) shifted the current reversal potential (V rev) from −2 ± 1 to +51 ± 3 mV (n = 15). In cells with predominant IR activity, in contrast, the same maneuver induced a shift of V rev to significantly larger (p ≤ 0.05, two-tailed t test) values (from −3 ± 1 to +66 ± 8 mV; n = 5) and an almost complete inhibition of outward current. The anion channel blocker NPPB reversibly decreased the ATP-generated OR currents from 1.1 ± 0.1 nS to 0.2 ± 0.05 nS and further shifted V rev to +87 ± 7 mV (n = 12). The NPPB-sensitive fraction of the OR reversed at +48 ± 4 mV suggesting a relative permeability of P ATP/P Cl ≈ 0.01. Together, these data raise the possibility that the OR might be the electrophysiological correlate of an erythrocyte ATP release pathway.

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Acknowledgements

This study was supported by the Deutsche Forschungsgemeinschaft Hu781/4–3.

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Tübingen, Germany

    Canan Akkaya, Ekaterina Shumilina, Diwakar Bobballa, Verena B. Brand, Hasan Mahmud & Florian Lang

  2. Department of Radiation Oncology, University of Tübingen, Tübingen, Germany

    Stephan M. Huber

  3. Department of Radiation Oncology, Eberhard-Karls-University Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    Stephan M. Huber

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  1. Canan Akkaya
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  2. Ekaterina Shumilina
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  3. Diwakar Bobballa
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Correspondence to Stephan M. Huber.

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Canan Akkaya and Ekaterina Shumilina contributed equally to this work and, thus, share first authorship.

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Akkaya, C., Shumilina, E., Bobballa, D. et al. The Plasmodium falciparum-induced anion channel of human erythrocytes is an ATP-release pathway. Pflugers Arch - Eur J Physiol 457, 1035–1047 (2009). https://doi.org/10.1007/s00424-008-0572-8

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