DECODING GLIOBLASTOMA INVASION: THE ROLE OF VOLTAGE-GATED POTASSIUM CHANNELS AND MICROTUBES IN POST-SURGICAL RECURRENCE

Abstract AIMS Isocitrate dehydrogenase wild-type glioblastoma (GBM) is an aggressive brain tumour with a high recurrence rate due to post-surgical residual disease. Poor prognosis is partly associated with infiltrative tumour cells forming networks with non-disease neural cells via electrical synapses, microtubes and tunnelling nanotubes, facilitating cellular communication and cargo transport. We hypothesise that voltage-gated potassium channels (VGKCs) in invasive GBM cells and associated microtubes could serve as therapeutic targets. This study aims to determine the presence and function of VGKCs and microtubes in GBM core and invasive margin cells. METHODS Patient-derived GBM core and invasive margin cells were analysed using Nanion’s Port-a-Patch to assess VGKC activity. Electrophysiological recordings were conducted with and without tetraethylammonium (TEA), a non- selective VGKC blocker, to determine channel selectivity. Live imaging for over 48 hours was performed using selective tubulin- and actin-targeting dyes for real-time visualisation of microtubule/microtube structures in both cell populations. Statistical analyses were conducted to compare electrical properties between the two groups. RESULTS Our results revealed that GBM cells from both intra-tumour regions exhibit functional VGKCs, with measurable currents modulated by TEA. Live imaging showed the transfer of microtubes upon proliferation, aiding in the movement of the cells. These findings suggest that VGKCs play an active role in GBM cell physiology and may contribute to the tumour’s electrical integration and invasive potential within the healthy brain. CONCLUSION These preliminary findings provide key insights into the functional behaviour of invasive margin GBM cells. More comprehensive VGKC characterisation will enhance our understanding of the excitable nature of GBM cells and the potential repurposing of drugs predicated upon this phenotype. Furthermore, structural and pro- tein analysis of microtubes will enhance our understanding of their composition and role in tumour progres- sion.