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Dissection of P2X4 and P2X7 Receptor Current Components in BV-2 Microglia
Authors:Mira Trang  Günther Schmalzing  Christa E Müller  Fritz Markwardt
Affiliation:1.Julius-Bernstein-Institute for Physiology, Martin-Luther-University, D-06097 Halle-Wittenberg, Germany; ;2.Institute of Clinical Pharmacology, RWTH Aachen University, D-52074 Aachen, Germany; ;3.Pharmaceutical Institute, Pharmaceutical & Mediinal Chemistry, University of Bonn, D-53121 Bonn, Germany;
Abstract:Microglia cells represent the immune system of the central nervous system. They become activated by ATP released from damaged and inflamed tissue via purinergic receptors. Ionotropic purinergic P2X4 and P2X7 receptors have been shown to be involved in neurological inflammation and pain sensation. Whether the two receptors assemble exclusively as homotrimers or also as heterotrimers is still a matter of debate. We investigated the expression of P2X receptors in BV-2 microglia cells applying the whole-cell voltage-clamp technique. We dissected P2X4 and P2X7 receptor-mediated current components by using specific P2X4 and P2X7 receptor blockers and by their characteristic current kinetics. We found that P2X4 and P2X7 receptors are activated independently from each other, indicating that P2X4/P2X7 heteromers are not of functional significance in these cells. The pro-inflammatory mediators lipopolysaccharide and interferon γ, if applied in combination, upregulated P2X4, but not P2X7 receptor-dependent current components also arguing against phenotypically relevant heteromerization of P2X4 and P2X7 receptor subunits.
Keywords:P2 purinergic receptor  P2X7 receptor  P2X4 receptor  voltage clamp  microglia
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