MODULATION OF CALCIUM OSCILLATIONS IN GLIOBLASTOMA: AN ELECTROPHYSIOLOGICAL APPROACH

Aims: Glioblastoma (GBM) is a highly aggressive brain tumour with a median survival of only 8-14 months despite standard therapy. One defining feature of GBM cells is their ability to form an interconnected network through calcium (Ca²⁺)-mediated communication. A subset of these cells (5-10%) shows spontaneous Ca²⁺ oscillations, which promote tumour progression even after surgical resection. These oscillations are regulated by a complex interplay of internal Ca²⁺ stores, store-operated Ca²⁺ channels, and Ca²⁺-activated potassium channels. The latter modulate the membrane potential, which regulates Ca²⁺ transport into the cells. In our novel approach, we aimed to modulate GBM Ca²⁺ oscillations using external electric interventions.
Methods: U87 cells stably expressing the NEMOc Ca²⁺ reporter were subjected to the external electrical field stimulation in a 2D monoculture, in a co-culture with organotypic brain slices, and as a 3D tumour grown on chick embryo chorioallantoic membrane (CAM). We used live microscopy to trace Ca²⁺ signalling in all models.
Results and Conclusions: In the monoculture, we observed an increase of Ca²⁺ oscillations following 0.1 Hz and 0.0167 Hz stimulation. In the co-culture and in the CAM model, alternating positive and negative fields (biphasic pulses at 100 Hz, ±2-10 mA) resulted in a large Ca²⁺ influx at the beginning of the stimulation, followed by focused oscillations throughout the session. After the stimulation ended, the oscillations ceased. These findings highlight the potential to manipulate GBM Ca²⁺ dynamics through targeted electrical interventions. Further research is needed to determine whether these approaches can influence tumour progression.