Potential therapeutic targeting of BKCa channels in glioblastoma treatment

Abstract

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 (BKCa) 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, BKCa channels are widely expressed in neurons, astrocytes, and oligodendrocytes, contributing to ion homeostasis and synaptic transmission. In glioblastoma cells, overexpression of BKCa channels, particularly the glioma-specific gBKCa variant, facilitates tumor progression by enhancing cell migration, invasion, and therapeutic resistance. Recent evidence highlights the significance of the mitochondrial isoform of the BKCa channel (mitoBKCa) 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 BKCa and mitoBKCa channels in glioblastoma biology, their potential classification as oncochannels, and the emerging pharmacological strategies targeting these channels, emphasizing the translational challenges in developing BKCa-directed therapies for glioblastoma treatment.