Extracellular Electrophysiology in the Prostate Cancer Cell Model PC-3

Abstract

Although prostate cancer is one of the most common cancers in the male population, its basic biological function at a cellular level remains to be fully understood. This lack of in depth understanding of its physiology significantly hinders the development of new, targeted and more effective treatment strategies. Whilst electrophysiological studies can provide in depth analysis, the possibility of recording electrical activity in large populations of non-neuronal cells remains a significant challenge, even harder to address in the picoAmpere-range, which is typical of cellular level electrical activities. In this paper, we present the measurement and characterization of electrical activity of populations of prostate cancer cells PC-3, demonstrating for the first time a meaningful electrical pattern. The low noise system used comprises a multi-electrode array (MEA) with circular gold electrodes on silicon oxide substrates. The extracellular capacitive currents present two standard patterns: an asynchronous sporadic pattern and a synchronous quasi-periodic biphasic spike pattern. An amplitude of ±150 pA, a width between 50–300 ms and an inter-spike interval around 0.5 Hz characterize the quasi-periodic spikes. Our experiments using treatment of cells with Gd3⁺, known as an inhibitor for the Ca2⁺ exchanges, suggest that the quasi-periodic signals originate from Ca2⁺ channels. After adding the Gd3⁺ to a population of living PC-3 cells, their electrical activity considerably decreased; once the culture was washed, thus eliminating the Gd3⁺ containing medium and addition of fresh cellular growth medium, the PC-3 cells recovered their normal electrical activity. Cellular viability plots have been carried out, demonstrating that the PC-3 cells remain viable after the use of Gd3⁺, on the timescale of this experiment. Hence, this experimental work suggests that Ca2⁺ is significantly affecting the electrophysiological communication pattern among PC-3 cell populations. Our measuring platform opens up new avenues for real time and highly sensitive investigations of prostate cancer signalling pathways.

Human Breast Cancer Cells Demonstrate Electrical Excitability

“…Our low-impedance electrodes make use of a large Helmholtz-Gouy-Chapman double-layer capacitance. The measured current signal is enhanced by the high sealing resistance between the confluent cell layer and the Au electrode, and by a gain factor proportional to the large electrode capacitance allowing for small-amplitude signals to be detected (Medeiros et al, 2016;Rocha et al, 2016a,b;Cabello et al, 2019).…”

Ultrasensitive System for Electrophysiology of Cancer Cell Populations: A Review

“…[44][45][46][47] The quasi-periodic spikes, however, were mostly characterized by larger signal magnitudes, with lower widths ranging from 0.03 to 0.3 s and the distance between spikes reaching a peak *2 to 3 s although the variation expands from 1 to 10 s of interval between biphasic spikes. 7 The spikes are larger and wider during the quasi-periodic activity, as expected for cooperative intracellular traveling waves. 15,17 We observed that the quasi-periodic nature of signals is slow and routinely occurs during prostate cancer proliferation.…”

“…Importantly, several controls have been made to ascertain that GdCl 3 is nontoxic to PC-3 cells during the experiments. 7 Our recent results reveal that one of the most common malignant cancers diagnosed in men can also be electrically monitored in real time and employed into our drug-screening platform. This could be quite advantageous as still little scientific understanding on the electrophysiology of prostate cancer growth and metastatic patterns exists.…”

“…Non-neuronal cancer-derived cells such as the gold standard of prostate cancer cell culture line, PC-3 cells, 3,7 glial cells, as well glia-derived glioma, which retain among others, the expression of neurotransmitter receptors and voltage-gated ion channels, do not exhibit unbiased action potentials. 8,9 Instead, those known to be electrically quiescent cells exhibit distinctive single-cell oscillations of the membrane potential.…”

Progress in the Knowledge, Application and Influence of Extremely Low Frequency Signals

“…A similar fact is observed in prostate cancer, one of the most common cancers in the male population, where its basic biological function at the cellular level is not yet fully known. In [81] the measurement and characterization of the electrical activity of PC-3 prostate cancer cell populations is presented, demonstrating for the first time the existence of a significant electrical pattern. This type of recording allows for the establishment of new, highly sensitive, real-time research pathways for the development of new, more-specific, and effective treatment strategies.…”