Ca²⁺ -activated K⁺ channels regulate cell volume in human glioblastoma cells

Glioblastoma (GBM), the most lethal form of brain tumors, bases its malignancy on the strong ability of its cells to migrate and invade the narrow spaces of healthy brain parenchyma. Cell migration and invasion are both critically dependent on changes in cell volume and shape driven by the transmembrane transport of osmotically important ions such as K⁺ and Cl^- . However, while the Cl^- channels participating in cell volume regulation have been clearly identified, the precise nature of the K⁺ channels involved is still uncertain. Using a combination of electrophysiological and imaging approaches in GBM U87-MG cells, we found that hypotonic-induced cell swelling triggered the opening of Ca²⁺ -activated K⁺ (K_Ca ) channels of large and intermediate conductance (BK_Ca and IK_Ca , respectively), both highly expressed in GBM cells. The influx of Ca²⁺ mediated by the hypotonic-induced activation of mechanosensitive channels was found to be a key step for opening both the BK_Ca and the IK_Ca channels. Finally, the activation of both K_Ca channels mediated by mechanosensitive channels was found to be essential for the development of the regulatory volume decrease following hypotonic shock. Taken together, these data indicate that K_Ca channels are the main K⁺ channels responsible for the volume regulation in U87-MG cells.