The interplay between α7 nicotinic acetylcholine receptors, pannexin-1 channels and P2X7 receptors elicit exocytosis in chromaffin cells

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dc.contributor.authorMaldifassi, María C.
dc.contributor.authorMomboisse, Fanny
dc.contributor.authorGuerra, María J.
dc.contributor.authorVielma, Alex H.
dc.contributor.authorMaripillán, Jaime
dc.contributor.authorBáez-Matus, Ximena
dc.contributor.authorFlores-Muñoz, Carolina
dc.contributor.authorCádiz, Bárbara
dc.contributor.authorSchmachtenberg, Oliver
dc.contributor.authorMartínez, Agustín D.
dc.contributor.authorCárdenas, Ana M.
dc.date.accessioned2022-11-30T02:46:31Z
dc.date.available2022-11-30T02:46:31Z
dc.date.issued2021
dc.description.abstractPannexin-1 (Panx1) forms plasma membrane channels that allow the exchange of small molecules between the intracellular and extracellular compartments, and are involved in diverse physiological and pathological responses in the nervous system. However, the signaling mechanisms that induce their opening still remain elusive. Here, we propose a new mechanism for Panx1 channel activation through a functional crosstalk with the highly Ca2+ permeable α7 nicotinic acetylcholine receptor (nAChR). Consistent with this hypothesis, we found that activation of α7 nAChRs induces Panx1-mediated dye uptake and ATP release in the neuroblastoma cell line SH-SY5Y-α7. Using membrane permeant Ca2+ chelators, total internal reflection fluorescence microscopy in SH-SY5Y-α7 cells expressing a membrane-tethered GCAMP3, and Src kinase inhibitors, we further demonstrated that Panx1 channel opening depends on Ca2+ signals localized in submembrane areas, as well as on Src kinases. In turn, Panx1 channels amplify cytosolic Ca2+ signals induced by the activation of α7 nAChRs, by a mechanism that seems to involve ATP release and P2X7 receptor activation, as hydrolysis of extracellular ATP with apyrase or blockage of P2X7 receptors with oxidized ATP significantly reduces the α7 nAChR-Ca2+ signal. The physiological relevance of this crosstalk was also demonstrated in neuroendocrine chromaffin cells, wherein Panx1 channels and P2X7 receptors contribute to the exocytotic release of catecholamines triggered by α7 nAChRs, as measured by amperometry. Together these findings point to a functional coupling between α7 nAChRs, Panx1 channels and P2X7 receptors with physiological relevance in neurosecretion.en_ES
dc.facultadFacultad de Cienciasen_ES
dc.file.nameMaldifassi_Int2021.pdf
dc.identifier.doihttps://doi.org/10.1111/jnc.15186
dc.identifier.urihttp://repositoriobibliotecas.uv.cl/handle/uvscl/7404
dc.languageen
dc.publisherWiley
dc.sourceJournal of Neurochemistry
dc.titleThe interplay between α7 nicotinic acetylcholine receptors, pannexin-1 channels and P2X7 receptors elicit exocytosis in chromaffin cells
dc.typeArticulo
uv.departamentoCentro Interdisciplinario de Neurociencia de Valparaiso

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