Modulation of suicidal erythrocyte cation channels by an AMPA antagonist
Michael Föller
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorHasan Mahmud
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorShuchen Gu
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorYuliya Kucherenko
Department of Physiology, University of Tübingen, Germany
Department of Cryobiophysics, Institute for Problems of Cryobiology and Cryomedicine of the NASc of Ukraine, Ukraine
Search for more papers by this authorEva-Maria Gehring
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorEkaterina Shumilina
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorElisa Floride
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorRolf Sprengel
Max-Planck-Institute for Neurobiology, Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Florian Lang
Department of Physiology, University of Tübingen, Germany
Correspondence to: Prof. Dr. Florian LANG, Physiologisches Institut der Universität Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.Tel.: +49 7071 29 72194Fax: +49 7071 29 5618E-mail: [email protected]Search for more papers by this authorMichael Föller
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorHasan Mahmud
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorShuchen Gu
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorYuliya Kucherenko
Department of Physiology, University of Tübingen, Germany
Department of Cryobiophysics, Institute for Problems of Cryobiology and Cryomedicine of the NASc of Ukraine, Ukraine
Search for more papers by this authorEva-Maria Gehring
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorEkaterina Shumilina
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorElisa Floride
Department of Physiology, University of Tübingen, Germany
Search for more papers by this authorRolf Sprengel
Max-Planck-Institute for Neurobiology, Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Florian Lang
Department of Physiology, University of Tübingen, Germany
Correspondence to: Prof. Dr. Florian LANG, Physiologisches Institut der Universität Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.Tel.: +49 7071 29 72194Fax: +49 7071 29 5618E-mail: [email protected]Search for more papers by this authorAbstract
In neurons alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are heteromeric cation channels composed of different sub-units, including GluA1-GluA4. When expressed without GluA2, AMPA receptors function as Ca2+-permeable cation channels. In erythrocytes, activation of Ca2+-permeable cation channels triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with subsequent exposure of phosphatidylserine at the cell surface. Activators of the channels and thus eryptosis include removal of extracellular Cl− (replaced by gluconate) and energy depletion (removal of glucose). The present study explored whether GluA1 is expressed in human erythrocytes and whether pharmacological AMPA receptor inhibition modifies Ca2+ entry and suicidal death of human erythrocytes. GluA1 protein abundance was determined by confocal microscopy, phosphatidylserine exposure was estimated from annexin V binding, cell volume from forward scatter in FACS analysis, cytosolic Ca2+ concentration from Fluo3 fluorescence and channel activity by whole-cell patch-clamp recordings. As a result, GluA1 is indeed expressed in the erythrocyte cell membrane. The AMPA receptor antagonist NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide) inhibited the cation channels following Cl− removal and the eryptosis following Cl− removal or energy depletion. The present study reveals a novel action of AMPA receptor antagonists and raises the possibility that GluA1 or a pharmacologically related protein participates in the regulation of Ca2+ entry into and suicidal death of human erythrocytes.
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