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Title: Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations
Authors: Rocha, Paulo R. F. 
Medeiros, Maria C. R. 
Kintzel, Ulrike
Vogt, Johannes
Araújo, Inês M. 
Mestre, Ana L. G.
Mailänder, Volker
Schlett, Paul
Dröge, Melanie
Schneider, Leonid
Biscarini, Fabio
de Leeuw, Dago M.
Gomes, Henrique L.
Keywords: ASICs; Acid-sensing ion channels; C6 Glioma; Electrical recording; Low frequency current noise; PcTX-1; bioelectronics; glia
Issue Date: Dec-2016
Publisher: American Association for the Advancement of Science
Project: European Commission, Seventh Framework Programme (FP7; 2007–2013), through project iONE FP7, grant agreement 280772 
Portuguese Foundation for Science and Technology (FCT) - project Intelligent Cell Surfaces EuroBioSAS/0001/2010, PEst-OE/EEI/LA0008/2013 
project Implantable Organic Devices for Advanced Therapies (INNOVATE) PTDC/EEI-AUT/5442/2014 
Serial title, monograph or event: Science Advances
Volume: 2
Issue: 12
Abstract: Glioma 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.
ISSN: 2375-2548
DOI: 10.1126/sciadv.1600516
Rights: openAccess
Appears in Collections:FCTUC Eng.Electrotécnica - Artigos em Revistas Internacionais
I&D IT - Artigos em Revistas Internacionais

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