Parabens inhibit hNaV 1.2 channels

dc.creatorEnrique, Andrea Verónica
dc.creatorMartín, Pedro
dc.creatorSbaraglini, María Laura
dc.creatorTalevi, Alan
dc.creatorMilesi, María Verónica
dc.date2020-08
dc.date2021-05-31T14:19:50Z
dc.date.accessioned2023-07-15T01:52:47Z
dc.date.available2023-07-15T01:52:47Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/119488
dc.identifierissn:0753-3322
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7459945
dc.descriptionPropylparaben, a commonly used antimicrobial preservative, has been reported as an anticonvulsant agent targeting neuronal Na+ channels (NaV). However, the specific features of the NaV channel inhibition by this agent have so far not been extensively studied. Moreover, it is still unclear if it shares this pharmacological activity with other parabens. Here, we fully characterized the mechanism of action of the inhibitory effect that propylparaben and benzylparaben induce on human NaV 1.2 channel isoform (hNaV1.2). We established a first approach to know the parabens structural determinants for this channel inhibition. The parabens effects on hNaV1.2 channel mediated currents were recorded using the patch-clamp whole-cell configuration on hNaV1.2 stably transfected HEK293 cells. Propylparaben induced a typical state-dependent inhibition on hNaV1.2 channel carried current, characterized by a left-shift in the steady-state inactivation curve, a prolongation in the time needed for recovery from fast inactivation and a frequency-dependent blocking behavior. The state-dependent inhibition is increased for butylparaben and benzylparaben and diminished for methylparaben, ethylparaben and p-hydroxybenzoic acid (the major metabolite of parabens hydrolysis). Particularly, butylparaben and benzylparaben shift the steady-state inactivation curve 2- and 3-times more than propylparaben, respectively. Parabens are blockers of hNaV1.2 channels, sharing the mechanism of action of most of sodium channel blocking antiseizure drugs. The potency of this inhibition increases with the size of the lipophilic alcoholic residue of the ester group. These results provide a basis for rational drug design directed to generate new potential anticonvulsant agents.
dc.descriptionInstituto de Estudios Inmunológicos y Fisiopatológicos
dc.descriptionLaboratorio de Investigación y Desarrollo de Bioactivos
dc.formatapplication/pdf
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.subjectBiología
dc.subjectPropylparaben
dc.subjectBenzylparaben
dc.subjectSodium channels
dc.subjecthNaV 1.2
dc.subjectAnticonvulsant drugs
dc.titleParabens inhibit hNaV 1.2 channels
dc.typeArticulo
dc.typeArticulo


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