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Neuropharmacology. 2013 Oct;73:122-37. doi: 10.1016/j.neuropharm.2013.05.017. Epub 2013 May 28.

P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone.

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  • 1Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.

Abstract

Neurogenesis requires the balance between the proliferation of newly formed progenitor cells and subsequent death of surplus cells. RT-PCR and immunocytochemistry demonstrated the presence of P2X7 receptor mRNA and immunoreactivity in cultured neural progenitor cells (NPCs) prepared from the adult mouse subventricular zone (SVZ). Whole-cell patch-clamp recordings showed a marked potentiation of the inward current responses both to ATP and the prototypic P2X7 receptor agonist dibenzoyl-ATP (Bz-ATP) at low Ca(2+) and zero Mg(2+) concentrations in the bath medium. The Bz-ATP-induced currents reversed their polarity near 0 mV; in NPCs prepared from P2X7(-/-) mice, Bz-ATP failed to elicit membrane currents. The general P2X/P2Y receptor antagonist PPADS and the P2X7 selective antagonists Brilliant Blue G and A-438079 strongly depressed the effect of Bz-ATP. Long-lasting application of Bz-ATP induced an initial current, which slowly increased to a steady-state response. In combination with the determination of YO-PRO uptake, these experiments suggest the dilation of a receptor-channel and/or the recruitment of a dye-uptake pathway. Ca(2+)-imaging by means of Fura-2 revealed that in a Mg(2+)-deficient bath medium Bz-ATP causes [Ca(2+)](i) transients fully depending on the presence of external Ca(2+). The MTT test indicated a concentration-dependent decrease in cell viability by Bz-ATP treatment. Correspondingly, Bz-ATP led to an increase in active caspase 3 immunoreactivity, indicating a P2X7-controlled apoptosis. In acute SVZ brain slices of transgenic Tg(nestin/EGFP) mice, patch-clamp recordings identified P2X7 receptors at NPCs with pharmacological properties identical to those of their cultured counterparts. We suggest that the apoptotic/necrotic P2X7 receptors at NPCs may be of particular relevance during pathological conditions which lead to increased ATP release and thus could counterbalance the ensuing excessive cell proliferation.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS:

2-MeSATP; 2-methylthio ATP; 2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate; 2′,3′-O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate; 3-(4,5-dimethylthioazol-2-yl)-2,5-diphenyltetrazoliumbromid; 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one; 5-BDBD; Adult neural progenitor cells; BBG; Brain subventricular zone; Brilliant Blue G; Bz-ATP; CNS; E(max); EC(50); EGF; Extracellular ATP; FGF-2; GAPDH; GFAP; MTT; Msi1; NPC; P2X7 receptors; PPADS; SVZ; TNP-ATP; X(2) concentration; [Ca(2+)](i); central nervous system; concentration of agonist producing 50% of E(max); divalent cation concentration; epidermal growth factor; fibroblast growth factor-2; glial fibrillary acidic protein; glyceraldehyde 3-phosphate dehydrogenase; intracellular Ca(2+) concentration; maximal effect; musashi1; neural progenitor cell; pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid; subventricular zone; wild-type; wt; α,β-meATP; α,β-methylene ATP

PMID:
23727220
[PubMed - indexed for MEDLINE]
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