Ca(2+)-activated K(+) (K(Ca)) channels are a unique family of
ion channels because they are capable of directly communicating
calcium signals to changes in cell membrane potential required for cellular processes including but not limited to cellular proliferation and migration. It is now possible to distinguish three families of K(Ca) channels based on differences in their biophysical and pharmacological properties as well as genomic sequence. Using a combination of biochemical, molecular, and biophysical approaches, we show that human
tumor cells of astrocytic origin, i.e.
glioma cells, express transcripts for all three family members of K(Ca) channels including BK, IK, and all three SK channel types (SK1, SK2, and SK3). The use of selective pharmacological inhibitors shows prominent expression of currents that are inhibited by the
BK channel specific inhibitors
iberiotoxin and
paxilline. However, despite the presence of transcripts for IK and SK, neither
clotrimazole, an inhibitor of IK channels, nor
apamin, known to block most SK channels inhibited any current. The exclusive expression of functional
BK channels was further substantiated by
shRNA knockdown experiments, which selectively reduced
iberiotoxin sensitive currents. Western blotting of patient biopsies with
antibodies specific for all three KCa channel types further substantiated the exclusive expression of BK type KCa channels in vivo. This finding is in sharp contrast to other
cancers that express primarily IK channels.