title: Purinergic signalling in a latent stem cell niche of the rat spinal cord.
abstract: The ependyma of the spinal cord harbours stem cells which are activated by traumatic spinal cord injury. Progenitor-like cells in the central canal (CC) are organized in spatial domains. The cells lining the lateral aspects combine characteristics of ependymocytes and radial glia (RG) whereas in the dorsal and ventral poles, CC-contacting cells have the morphological phenotype of RG and display complex electrophysiological phenotypes. The signals that may affect these progenitors are little understood. Because ATP is massively released after spinal cord injury, we hypothesized that purinergic signalling plays a part in this spinal stem cell niche. We combined immunohistochemistry, in vitro patch-clamp whole-cell recordings and Ca(2+) imaging to explore the effects of purinergic agonists on ependymal progenitor-like cells in the neonatal (P1-P6) rat spinal cord. Prolonged focal application of a high concentration of ATP (1 mM) induced a slow inward current. Equimolar concentrations of BzATP generated larger currents that reversed close to 0 mV, had a linear current-voltage relationship and were blocked by Brilliant Blue G, suggesting the presence of functional P2X7 receptors. Immunohistochemistry showed that P2X7 receptors were expressed around the CC and the processes of RG. BzATP also generated Ca(2+) waves in RG that were triggered by Ca(2+) influx and propagated via Ca(2+) release from internal stores through activation of ryanodine receptors. We speculate that the intracellular Ca(2+) signalling triggered by P2X7 receptor activation may be an epigenetic mechanism to modulate the behaviour of progenitors in response to ATP released after injury.
authors.affiliation: Neurofisiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP 11600, Montevideo, Uruguay.|Adult Neurogenesis and Cellular Reprogramming, Institute of Physiological Chemistry, Johannes Gutenberg University, Hanns-Dieter-Husch-Weg 19, Mainz, 55128, Germany.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Marichal
authors.affiliation: Neurofisiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP 11600, Montevideo, Uruguay.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Fabbiani
authors.affiliation: Neurofisiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP 11600, Montevideo, Uruguay.
authors.forename: Omar
authors.initials: O
authors.lastname: Trujillo-Cenóz
authors.affiliation: Neurofisiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP 11600, Montevideo, Uruguay. rrusso@iibce.edu.uy.
authors.forename: Raúl E
authors.initials: RE
authors.lastname: Russo
mesh_terms: D000255:Adenosine Triphosphate / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology
chemical_list: D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate
keywords: Ca2+ waves; Ependyma; P2X7 receptors; Purinergic signalling; Spinal cord; Stem cells