title: Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations.
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.
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany.
authors.forename: Paulo R F
authors.identifier: 0000-0002-8917-9101
authors.initials: PR
authors.lastname: Rocha
authors.affiliation: Instituto de Telecomunicações, Departamento de Engenharia Electrotécnica e de Computadores, Universidade de Coimbra, 3030-290 Coimbra, Portugal.
authors.forename: Maria C R
authors.initials: MC
authors.lastname: Medeiros
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany.
authors.forename: Ulrike
authors.identifier: 0000-0003-3231-9481
authors.initials: U
authors.lastname: Kintzel
authors.affiliation: Institute of Microanatomy and Neurobiology, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogt
authors.affiliation: Department of Biomedical Sciences and Medicine, University of Algarve, 8005-139 Faro, Portugal.; Centre for Biomedical Research, University of Algarve, 8005-139 Faro, Portugal.
authors.forename: Inês M
authors.initials: IM
authors.lastname: Araújo
authors.affiliation: Instituto de Telecomunicações, Avenida Rovisco, Pais 1, 1049-001 Lisboa, Portugal.; Universidade do Algarve, Faculdade de Ciências e Tecnologia, 8005-139 Faro, Portugal.
authors.forename: Ana L G
authors.identifier: 0000-0002-6679-8698
authors.initials: AL
authors.lastname: Mestre
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany.; Dermatology Clinic, University Medicine of the Johannes-Gutenberg Universität Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mailänder
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Schlett
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Dröge
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany.
authors.forename: Leonid
authors.identifier: 0000-0002-6204-9470
authors.initials: L
authors.lastname: Schneider
authors.affiliation: Department of Life Sciences, Università di Modena e Reggio Emilia, Via Campi 103, I-41125 Modena, Italy.
authors.forename: Fabio
authors.identifier: 0000-0001-6648-5803
authors.initials: F
authors.lastname: Biscarini
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany.; Faculty of Aerospace Engineering, Delft University of Technology, Kluyverweg 1, 2629 HS, Delft, Netherlands.
authors.forename: Dago M
authors.initials: DM
authors.lastname: de Leeuw
authors.affiliation: Instituto de Telecomunicações, Avenida Rovisco, Pais 1, 1049-001 Lisboa, Portugal.; Universidade do Algarve, Faculdade de Ciências e Tecnologia, 8005-139 Faro, Portugal.
authors.forename: Henrique L
authors.identifier: 0000-0003-3664-4740
authors.initials: HL
authors.lastname: Gomes
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D055724:Electrophysiological Phenomena; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009415:Nerve Net; D009474:Neurons / Q000166:cytology*; D051381:Rats; D015222:Sodium Channels / Q000502:physiology
chemical_list: D015222:Sodium Channels
keywords: ASICs; Acid-sensing ion channels; C6 Glioma; Electrical recording; Low frequency current noise; PcTX-1; bioelectronics; glia