Por favor, use este identificador para citar o enlazar este ítem:
https://www.arca.fiocruz.br/handle/icict/23544
Tipo
ArtículoDerechos de autor
Acceso restringido
Fecha del embargo
2030-01-01
Colecciones
- IOC - Artigos de Periódicos [12642]
Metadatos
Mostrar el registro completo del ítem
P2X7 RECEPTOR LARGE PORE SIGNALING IN AVIAN MÜLLER GLIAL CELLS
Bico
Formação de poros
Captação de tinta
Células gliais de Müller
Sinalização intracelular
Pore formation
Dye uptake
Avian
Müller glial cells
Intracellular signaling
Afiliación
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxoplasmose. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neuroquímica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neuroquímica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neuroquímica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Neuroquímica. Rio de Janeiro, RJ, Brasil.
Resumen en ingles
ATP is a pleiotropic molecule that promotes extra- and intracellular signaling to regulate numerous functions. This nucleotide activates purine and pyrimidine receptors at the plasma membrane, categorized as ionotropic P2X or G-protein-coupled receptor (GPCR) P2Y receptors. P2X are ligand-gated ion channel receptors, expressed in both retinal neurons and Müller cells leading to neuron-glia communication, calcium waves and neurovascular coupling. However, how P2X pore is formed upon ATP activation and how signaling pathways regulates the complex is still a matter of controversy. Here we studied the properties of the P2X7 receptor (P2X7R) using electrophysiology, single cell Ca2+ imaging, and dye uptake assay in purified avian Müller glia in culture. Our data show that ATP (or benzoyl-benzoyl ATP, BzATP) evoked large inward currents in patch-clamp studies while addition of P2X7R antagonist such as brilliant Blue G (BBG), abolished these currents. Ruthenium red (RU-2), a general transient receptor potential (TRP) inhibitor, reduced currents induced by ATP. Our data also point to the involvement of mitogen activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), Ca2+-calmodulin kinase II (CAMKII), microtubules or protein kinase C (PKC) modulating ATP-induced ionic current in Müller cells. We show that ATP induced Ca2+ influx, partially inhibited by P2X7R antagonists (oxidized ATP or BBG), and totally inhibited by blockers of other pores such as transient receptor potential (TRPs) or connexin hemichannel. Additionally, MAPK, PKC, PI3K or CAMKII inhibitors also are involved in the modulation of intracellular calcium signaling. Finally, ATP induced 80-90% of dye uptake in Muller glia cells, while oxidized ATP (oATP), BBG or A740003 inhibited this effect. We conclude that large conductance channel and other P2XRs are not involved in the ATP-induced dye uptake, but signaling pathways such as MAPK, PI3-K, microtubules or PKC are involved in pore formation.
Palabras clave en portugues
Receptores Purinérgicos P2X7Bico
Formação de poros
Captação de tinta
Células gliais de Müller
Sinalização intracelular
Palabras clave en ingles
P2X7 receptorPore formation
Dye uptake
Avian
Müller glial cells
Intracellular signaling
Compartir