Targeting Ca-activated K channels in glioma.

Glioma affects millions of people worldwide and there is a lack of effective therapies. Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor in adults. Emerging evidence indicated that targeting ion channels may be a promising therapeutic approach for GBM. Altered expression and activity of the Ca- activated K (K) channels have been reported in GBM patients. Generally, large-conductance K (BK) channels and intermediate-conductance K (IK or SK4) channels are highly expressed in glioma samples compared to healthy control brain tissue. Analyzing TCGA database, the expression of KCNMB1 (encoding the BK channel protein) and KCNN4 (encoding the K3.1/IK protein) genes was upregulated, while KCNN1 (encoding the K2.1 protein) gene expression was downregulated in GBM patients grade IV compared to GBM patients grade I or II. The gene expression and activity of K channels may contribute to survival outcomes, by regulating cellular processes like cell proliferation and migration. Importantly, modulation of the activity of K channels reduced the proliferation and migration of GBM cells and suppressed glioma progression both in vivo and in vitro cell models for GBM. Herein, we aim to review how modulation of the activity of K channels impacts tumor development in terms of proliferation, cell death, invasion, metabolism and immune system in GBM.