Diflunisal inhibits prestin by chloride-dependent mechanism

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dc.citation.articleNumbere0183046
dc.citation.issueNumber8
dc.citation.journalTitlePLoS ONE
dc.citation.volumeNumber12
dc.contributor.authorDuret, Guillaume
dc.contributor.authorPereira, Fred A.
dc.contributor.authorRaphael, Robert M.
dc.date.accessioned2017-09-19T18:39:59Z
dc.date.available2017-09-19T18:39:59Z
dc.date.issued2017
dc.description.abstractThe motor protein prestin is a member of the SLC26 family of anion antiporters and is essential to the electromotility of cochlear outer hair cells and for hearing. The only direct inhibitor of electromotility and the associated charge transfer is salicylate, possibly through direct interaction with an anion-binding site on prestin. In a screen to identify other inhibitors of prestin activity, we explored the effect of the non-steroid anti-inflammatory drug diflunisal, which is a derivative of salicylate. We recorded prestin activity by whole-cell patch clamping HEK cells transiently expressing prestin and mouse outer hair cells. We monitored the impact of diflunisal on the prestin-dependent non-linear capacitance and electromotility. We found that diflunisal triggers two prestin-associated effects: a chloride independent increase in the surface area and the specific capacitance of the membrane, and a chloride dependent inhibition of the charge transfer and the electromotility in outer hair cells. We conclude that diflunisal affects the cell membrane organization and inhibits prestin-associated charge transfer and electromotility at physiological chloride concentrations. The inhibitory effects on hair cell function are noteworthy given the proposed use of diflunisal to treat neurodegenerative diseases.
dc.identifier.citationDuret, Guillaume, Pereira, Fred A. and Raphael, Robert M.. "Diflunisal inhibits prestin by chloride-dependent mechanism." <i>PLoS ONE,</i> 12, no. 8 (2017) Public Library of Science: https://doi.org/10.1371/journal.pone.0183046.
dc.identifier.digitalDiflunisal_inhibits_prestin
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0183046
dc.identifier.urihttps://hdl.handle.net/1911/97403
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleDiflunisal inhibits prestin by chloride-dependent mechanism
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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