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

Rocha, R.F ; Medeiros, M. C. R. ; Kintzel, Ulrike ; Vogt, Johannes ; Araújo , I ; Mestre, A. G. ; Mailänder, Volker ; Schlett, Paul ; Dröge, Melanie ; Schneider, Leonid ; Biscarini, F. ; de Leeuw, D.D.M. ; Gomes, H.L.

Science advances Vol. 2, Nº 12, pp. e1600516 - e1600516, December, 2016.

ISSN (print): 2375-2548
ISSN (online):

Scimago Journal Ranking: 4,80 (in 2016)

Digital Object Identifier: 10.1126/sciadv.1600516

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.