Cloning and Characterization of Glioma BK, a Novel BK Channel Isoform Highly Expressed in Human Glioma Cells

摘要: Voltage-dependent large-conductance Ca 2+ -activated K + channels (BK channels) are widely expressed in excitable and nonexcitable cells. BK exhibit diverse electrophysiological properties, which attributable part to alternative splicing of their α-subunits. currents have been implicated the growth control glial cells, with novel biophysical properties recently characterized human glioma Here we report isolation, cloning, functional characterization (gBK), a splice isoform hSlo , gene that encodes α-subunits channels. The primary sequence gBK is 97% identical its closest homolog hbr5, but it contains an additional 34-amino-acid exon at site 2 C-terminal tail transcripts containing this ubiquitously various normal tissues as well neoplasmic samples, suggesting may modulate important physiological functions Expression Xenopus oocytes gives rise iberiotoxin-sensitive (IbTX) currents, IC 50 for IbTX 5.7 nm Hill coefficient 0.76. Single unitary conductance ∼250 pS, show significantly slower activation higher sensitivity than hbr5. was enhanced specifically physiologically relevant [Ca ] i (100–500 nm). Examination biopsies from patients malignant gliomas has revealed specific overexpression compared nonmalignant cortical tissues. Importantly, tumor malignancy grades correlated positively channel expression, role biology.