Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation

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dc.contributor.authorLillo, Mauricio A.
dc.contributor.authorGaete, Pablo S.
dc.contributor.authorPuebla, Mariela
dc.contributor.authorBurboa, Pia C.
dc.contributor.authorPoblete, Ines
dc.contributor.authorFigueroa, Xavier F.
dc.date.accessioned2025-01-20T23:52:22Z
dc.date.available2025-01-20T23:52:22Z
dc.date.issued2021
dc.description.abstractDeletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca2+](i) of endothelial cells. Changes in NO-mediated vasodilation, membrane potential, superoxide anion (O-2(-)) formation, and endothelial cell [Ca2+](i) were analyzed in rat isolated mesenteric arterial beds and primary cultures of mesenteric endothelial cells. Inhibition of Panx-1 channels with probenecid (1 mM) or the Panx-1 blocking peptide (10)Panx (60 mu M) evoked an increase in the ACh (100 nM)-induced vasodilation of KCl-contracted mesenteries and in the phosphorylation level of endothelial NO synthase (eNOS) at serine 1177 (P-eNOS(S1177)) and Akt at serine 473 (P-Akt(S473)). In addition, probenecid or (10)Panx application activated a rapid, tetrodotoxin (TTX, 300 nM)-sensitive, membrane potential depolarization and [Ca2+](i) increase in endothelial cells. Interestingly, the endothelial cell depolarization was converted into a transient spike after removing Ca2+ ions from the buffer solution and in the presence of 100 mu M mibefradil or 10 mu M Ni2+. As expected, Ni2+ also abolished the increment in [Ca2+](i). Expression of Na(v)1.2, Na(v)1.6, and Ca(v)3.2 isoforms of voltage-dependent Na+ and Ca2+ channels was confirmed by immunocytochemistry. Furthermore, the Panx-1 channel blockade was associated with an increase in O-2(-) production. Treatment with 10 mu M TEMPOL or 100 mu M apocynin prevented the increase in O-2(-) formation, ACh-induced vasodilation, P-eNOS(S1177), and P-Akt(S473) observed in response to Panx-1 inhibition. These findings indicate that the Panx-1 channel blockade triggers a novel complex signaling pathway initiated by the sequential activation of TTX-sensitive Na-v channels and Ca(v)3.2 channels, leading to an increase in NO-mediated vasodilation through a NADPH oxidase-dependent P-eNOS(S1177), which suggests that Panx-1 may be involved in the endothelium-dependent control of arterial blood pressure.
dc.fuente.origenWOS
dc.identifier.doi10.1155/2021/2678134
dc.identifier.eissn1942-0994
dc.identifier.issn1942-0900
dc.identifier.urihttps://doi.org/10.1155/2021/2678134
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94908
dc.identifier.wosidWOS:000625328600004
dc.language.isoen
dc.revistaOxidative medicine and cellular longevity
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNovel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation
dc.typeartículo
dc.volumen2021
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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