Mapping the functional expression of auxiliary subunits of K(Ca)1.1 in glioblastoma

Glioblastoma (GBM) is the most aggressive glial tumor, where ion channels, including K(Ca)1.1, are candidates for new therapeutic options. Since the auxiliary subunits linked to K(Ca)1.1 in GBM are largely unknown we used electrophysiology combined with pharmacology and gene silencing to address the functional expression of K(Ca)1.1/β subunits complexes in both primary tumor cells and in the glioblastoma cell line U-87 MG. The pattern of the sensitivity (activation/inhibition) of the whole-cell currents to paxilline, lithocholic acid, arachidonic acid, and iberiotoxin; the presence of inactivation of the whole-cell current along with the loss of the outward rectification upon exposure to the reducing agent DTT collectively argue that K(Ca)1.1/β3 complex is expressed in U-87 MG. Similar results were found using human primary glioblastoma cells isolated from patient samples. Silencing the β3 subunit expression inhibited carbachol-induced Ca(2+) transients in U-87 MG thereby indicating the role of the K(Ca)1.1/β3 in the Ca(2+) signaling of glioblastoma cells. Functional expression of the K(Ca)1.1/β3 complex, on the other hand, lacks cell cycle dependence. We suggest that the K(Ca)1.1/β3 complex may have diagnostic and therapeutic potential in glioblastoma in the future.