Voltage-Gated Proton Channel in Human Glioblastoma Multiforme Cells

Solid tumors tend to have a more glycolytic metabolism leading to an accumulation of acidic metabolites in their cytosol, and consequently, their intracellular pH (pH(i)) turns critically lower if the cells do not handle the acid excess. Recently, it was proposed that the voltage gated proton channels (H(v)1) can regulate the pH(i) in several cancers. Here we report the functional expression of voltage gated proton channels in a human glioblastoma multiforme (GBM) cell line, the most common and lethal brain tumor. T98G cells presented an outward, slow activating voltage-dependent proton current, which was also Delta pH-dependent and inhibited by ZnCl2, characterizing it as being conducted by H(v)1 channels. Furthermore, blocking H(v)1 channels with ZnCl2 significantly reduced the pH(i), cell survival, and migration, indicating an important role for H(v)1 for tumor proliferation and progression in GBM. Overall, our results suggest that H(v)1 channels can be a new therapeutic target for GBM.