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Electrophysiological characteristics, molecular identity, regulation and physiological role of membrane anionic channels of the human erythrocyte in health and disease

Abstract : Red blood cells are a classic model system for studying how ions, nutrients and other solutes cross the plasma membrane. Molecular identity, regulation and physiological role of anionic channels are unclear, in spite of the evidences of their involvement in the physiological process of senescence of RBCs, as well as in pathological conditions such as sickle cell disease or malaria. The present work, using patch-clamp electrophysiological technique and biochemical assays shows that: 1/ The diversity of anionic channel activities recorded in normal, as well as in Plasmodium falciparum-infected human erythrocytes, corresponds to different kinetic modalities of a unique type of maxi-anion channel with multiply conductance levels, gating properties and pharmacology, depending on conditions. 2/ The molecular identity of these anionic channels corresponds to the voltage-dependent anion channel (VDAC), one of the component of the peripheral-type benzodiazepine receptor (PBR) present in the RBCs membrane. 3/ The dormant, endogenous VDAC becomes the "new permeability pathways" in infected erythrocytes after up-regulation by P.falciparum and is modulated by the Ring-infected Erythrocyte Surface Antigen (RESA), protein exported by the parasite to the host RBC membrane. Finally, the present work contributes to the understanding of the specific role played by the ionic channels in the RBCs membrane, both in health and disease. It shows that it would be simplistic to consider that these channels are relics or residues of a lost previous function during evolution or maturation process of erythrocytes.
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Submitted on : Monday, June 3, 2013 - 12:04:20 PM
Last modification on : Sunday, June 26, 2022 - 5:25:56 AM
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  • HAL Id : tel-00829430, version 1

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Edyta Glogowska. Electrophysiological characteristics, molecular identity, regulation and physiological role of membrane anionic channels of the human erythrocyte in health and disease. Cellular Biology. Université Pierre et Marie Curie - Paris VI, 2012. English. ⟨NNT : 2012PAO66397⟩. ⟨tel-00829430⟩

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