TRPC6 interacted with K1.1 channels to regulate the proliferation and apoptosis of glioma cells.

Malignant glioma is the most aggressive and deadliest brain malignancy. TRPC6 and K1.1, two ion channels, have been considered as potential therapeutic targets for malignant glioma treatment. TRPC6, a Ca-permeable channel, plays a vital role in promoting tumorigenesis and the progression of glioma. K1.1, a large-conductance Ca-activated channel, is also involved in growth and migration of glioma. However, the underlying mechanism by which these two ion channels promote glioma progression was unclear. In our study, we found that TRPC6 upregulated the expression of K1.1, while the immunoprecipitation analysis also showed that TRPC6 interacts with K1.1 channels in glioma cells. The currents of K1.1 recorded by the whole-cell patch clamp technique were increased by TRPC6 in glioma cells, suggesting that TRPC6 can provide a Ca source for the activation of K1.1 channels. It was also suggested that TRPC6 regulates the proliferation and apoptosis of glioma cells through K1.1 channels in vitro. Therefore, C6-bearing glioma rats were established to validate the results in vitro. After the administration of paxilline (a specific inhibitor of K1.1 channels), TRPC6-dependent growth of glioma was inhibited in vivo. We also found that TRPC6 enhanced co-expression with K1.1 in glioma. These all suggested that TRPC6/K1.1 signal plays a role in promoting the growth of glioma. Our results provided new evidence for TRPC6 and K1.1 as potential targets for glioma treatment.