Potential therapeutic targeting of BK _Ca channels in glioblastoma treatment

Potassium channels in brain tissue orchestrate essential cellular processes, including the regulation of membrane potential and neuronal excitability. Among them, large-conductance calcium-activated potassium (BK_Ca) channels play a pivotal role in both normal brain physiology and the pathogenesis of glioblastoma multiforme, a highly aggressive primary brain tumor. Within the central nervous system, BK_Ca channels are widely expressed in neurons, astrocytes, and oligodendrocytes, contributing to ion homeostasis and synaptic transmission. In glioblastoma cells, overexpression of BK_Ca channels, particularly the glioma-specific gBK_Ca variant, facilitates tumor progression by enhancing cell migration, invasion, and therapeutic resistance. Recent evidence highlights the significance of the mitochondrial isoform of the BK_Ca channel (mitoBK_Ca) in modulating oxidative phosphorylation and reactive oxygen species generation, thereby promoting tumor cell survival under hypoxic and cytotoxic stress. This review summarizes current insights into the role of BK_Ca and mitoBK_Ca channels in glioblastoma biology, their potential classification as oncochannels, and the emerging pharmacological strategies targeting these channels, emphasizing the translational challenges in developing BK_Ca-directed therapies for glioblastoma treatment.