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Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations

2016-12Journal article Open Access
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dc.contributor.authorRocha, Paulo R. F.
dc.contributor.authorMedeiros, Maria C. R.
dc.contributor.authorKintzel, Ulrike
dc.contributor.authorVogt, Johannes
dc.contributor.authorAraújo, Inês
dc.contributor.authorMestre, Ana L. G.
dc.contributor.authorMailaender, Volker
dc.contributor.authorSchlett, Paul
dc.contributor.authorDroege, Melanie
dc.contributor.authorSchneider, Leonid
dc.contributor.authorBiscarini, Fabio
dc.contributor.authorde Leeuw, Dago M.
dc.contributor.authorGomes, Henrique L.
dc.date.accessioned2017-04-07T15:55:37Z
dc.date.available2017-04-07T15:55:37Z
dc.date.issued2016-12
dc.description.abstractGlioma patients often suffer from epileptic seizures because of the tumor's impact on the brain physiology. Using the rat glioma cell line C6 as a model system, we performed long-term live recordings of the electrical activity of glioma populations in an ultrasensitive detection method. The transducer exploits large-area electrodes that maximize double-layer capacitance, thus increasing the sensitivity. This strategy allowed us to record glioma electrical activity. We show that although glioma cells are nonelectrogenic, they display a remarkable electrical burst activity in time. The low-frequency current noise after cell adhesion is dominated by the flow of Na+ ions through voltage-gated ion channels. However, after an incubation period of many hours, the current noise markedly increased. This electric bursting phenomenon was not associated with apoptosis because the cells were viable and proliferative during the period of increased electric activity. We detected a rapid cell culture medium acidification accompanying this event. By using specific inhibitors, we showed that the electrical bursting activity was prompted by extracellular pH changes, which enhanced Na+ ion flux through the psalmotoxin 1-sensitive acid-sensing ion channels. Our model of pH-triggered bursting was unambiguously supported by deliberate, external acidification of the cell culture medium. This unexpected, acidosis-driven electrical activity is likely to directly perturb, in vivo, the functionality of the healthy neuronal network in the vicinity of the tumor bulk and may contribute to seizures in glioma patients.
dc.identifier.doi10.1126/sciadv.1600516
dc.identifier.issn2375-2548
dc.identifier.otherAUT: HGO00803;
dc.identifier.urihttp://hdl.handle.net/10400.1/9177
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Association for the Advancement of Science
dc.relationImplantable Organic Nano-Electronics
dc.relationIntelligent Cell Surfaces (ICS)
dc.relationIMPLANTABLE ORGANIC DEVICES FOR ADVANCED THERAPIES (INNOVATE)
dc.relation.isbasedonWOS:000391268800006
dc.titleExtracellular electrical recording of pH-triggered bursts in C6 glioma cell populations
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleImplantable Organic Nano-Electronics
oaire.awardTitleIntelligent Cell Surfaces (ICS)
oaire.awardTitleIMPLANTABLE ORGANIC DEVICES FOR ADVANCED THERAPIES (INNOVATE)
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/280772/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EuroBioSAS%2F0001%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PEst-OE%2FEEI%2FLA0008%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FEEI-AUT%2F5442%2F2014/PT
oaire.citation.endPagee1600516
oaire.citation.issue12
oaire.citation.startPagee1600516
oaire.citation.titleScience Advances
oaire.citation.volume2
oaire.fundingStreamFP7
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
person.familyNamePombinho de Araújo
person.familyNameGomes
person.givenNameInês Maria
person.givenNameHenrique Leonel
person.identifierF-4703-2012
person.identifier.ciencia-idD11F-D4CA-2947
person.identifier.orcid0000-0002-2438-0111
person.identifier.orcid0000-0003-3664-4740
person.identifier.scopus-author-id56271084100
person.identifier.scopus-author-id7005305880
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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