Low frequency electric current noise in glioma cell populations

Abstract

aeMeasuring the electrical activity of large and defined populations of cells is currently a major technical challenge to electrophysiology, especially in the picoampere-range. For this purpose, we developed and applied a bidirectional transducer based on a chip with interdigitated gold electrodes to record the electrical response of cultured glioma cells. Recent research determined that also non-neural brain glia cells are electrically active and excitable. Their transformed counterparts, e.g. glioma cells, were suggested to partially retain these electric features. Such electrophysiological studies however are usually performed on individual cells and are limited in their predictive power for the overall electrical activity of the multicellular tumour bulk. Our extremely low-noise measuring system allowed us to detect not only prominent electrical bursts of neuronal cells but also minute, yet constantly occurring and functional, membrane capacitive current oscillations across large populations of C6 glioma cells, which we termed electric current noise.At the same time, tumour cells of non-brain origin (HeLa) proved to be electrically quiescent in comparison.Finally, we determined that the glioma cell activity is primarily caused by the opening of voltage-gated Na + and K + ion channels and can be efficiently abolished using specific pharmacological inhibitors. Thus, we offer here a unique approach for studying electrophysiological properties of large cancer cell populations as an in vitro reference for tumour bulks in vivo.

Ultrasensitive System for Electrophysiology of Cancer Cell Populations: A Review

“…In addition, the thermal contribution of the cell noise vanishes as the original S I becomes re-established. 16 We concluded that freshly adhered C6 glioma cells produced a basal current noise of a few picoampheres and this residual activity was influenced by the flow of Na + ions through their respective voltage-gated channels. 16…”

“…17 Thus, by minimizing the background noise through the use of low impedance large area electrodes and by minimizing external interferences using a set of Faraday's cages around the measurement equipment, we have shown that the noise level can be reduced from conventional 10-100 lVpp to only 0.3 lVpp. 15,16 We note that the signals recorded using our large electrode area are the sum of all individual cell contributions. We estimate *25,000 cells adhered to a 10.5 mm 2 electrode.…”

“…The current noise level revealed a small value of only 100 fA. 16 As a control experiment, we employed a human cervical carcinoma cell line HeLa, because these cells did not originate from the brain nor from any other electrically active tissue. Yet, owing to the high sensitivity of our system, we could even detect residual fluctuations of their basal current level ( Fig.…”

“…Fluctuations near 3 pA were detected and differences between C6 and HeLa cells was reported. 16 C6 glioma cells were chosen as they were a robust and available model to validate the detection system. In fact, the current noise fluctuations of C6 glioma cells are comparatively larger than that of HeLa cells.…”

“…13 As the electrical activity of non-neuronal cells is minute and difficult to detect, we have derived ultrasensitive electrical transducers to enable electrophysiological recordings. 14,15 In this study, we review our recent advances in sensitive transducers to decode cancer cell-cell communication with emphasis on pH-sensitive rat C6 glioma cells 16,17 and human prostate cancer cell model PC-3. 7…”