Extracellular gentamicin reduces the activity of con nexin hemichannels and interferes with purinergic Ca<SUP>2+</SUP> signaling in HeLa cells

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dc.contributor.authorFigueroa, Vania A.
dc.contributor.authorRetamal, Mauricio A.
dc.contributor.authorCea, Luis A.
dc.contributor.authorSalas, Jose D.
dc.contributor.authorVargas, Anibal A.
dc.contributor.authorVerdugo, Christian A.
dc.contributor.authorJara, Oscar
dc.contributor.authorMartinez, Agustin D.
dc.contributor.authorSaez, Juan C.
dc.date.accessioned2025-01-23T21:41:16Z
dc.date.available2025-01-23T21:41:16Z
dc.date.issued2014
dc.description.abstractGap junction channels (GJCs) and hemichannels (HCs) are composed of protein subunits termed connexins (Cxs) and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the adenosine triphosphate release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects.
dc.fuente.origenWOS
dc.identifier.doi10.3389/fncel.2014.00265
dc.identifier.issn1662-5102
dc.identifier.urihttps://doi.org/10.3389/fncel.2014.00265
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101637
dc.identifier.wosidWOS:000344462100001
dc.language.isoen
dc.revistaFrontiers in cellular neuroscience
dc.rightsacceso restringido
dc.subjectaminoglycosides
dc.subjectconnexins
dc.subjectCx26
dc.subjectdye uptake
dc.subjectmembrane current
dc.subjectintracellular calcium
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleExtracellular gentamicin reduces the activity of con nexin hemichannels and interferes with purinergic Ca<SUP>2+</SUP> signaling in HeLa cells
dc.typeartículo
dc.volumen8
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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