Role for calcium‐activated potassium channels (BK) in growth control of human malignant glioma cells
- 13 September 2004
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 78 (2), 224-234
- https://doi.org/10.1002/jnr.20240
Abstract
Voltage‐dependent large‐conductance Ca2+‐activated K+ channels, often referred to as BK channels, are a unique class of ion channels coupling intracellular chemical signaling to electrical signaling. BK channel expression has been shown to be up‐regulated in human glioma biopsies, and expression levels correlate positively with the malignancy grade of the tumor. Glioma BK channels (gBK) are a splice variant of the hslo gene, are characterized by enhanced sensitivity to [Ca2+]i, and are the target of modulation by growth factors. By using the selective pharmacological BK channel inhibitor iberiotoxin, we examined the potential role of these channels in tumor growth. Cell survival assays examined the ability of glioma cells to grow in nominally serum‐free medium. Under such conditions, BK channel inhibition by iberiotoxin caused a dose‐ and time‐dependent decrease in cell number discernible as early as 72 hr after exposure and maximal growth inhibition after 4–5 days. FACS analysis shows that IbTX treatment arrests glioma cells in S phase of the cell cycle, whereupon cells undergo cell death. Interestingly, IbTX effects were nullified when cells were maintained in 7% fetal calf serum. Electrophysiological analysis, in conjunction with biotinylation studies, demonstrates that serum starvation caused a significant translocation of BK channel protein to the plasma membrane, corresponding to a two‐ to threefold increase in whole‐cell conductance, but without a change in total gBK protein. Hence, expression of functional gBK channels appears to be regulated in a growth‐factor‐dependent manner, with enhanced surface expression promoting tumor cell growth under conditions of growth factor deprivation as might occur under in vivo conditions.Keywords
This publication has 57 references indexed in Scilit:
- Unexpected Down-regulation of the hIK1 Ca2+-activated K+ Channel by Its Opener 1-Ethyl-2-benzimidazolinone in HaCaT KeratinocytesPublished by Elsevier BV ,2003
- BK channels in human glioma cells have enhanced calcium sensitivityGlia, 2002
- Autocrine and paracrine signaling through neuropeptide receptors in human cancerOncogene, 2001
- Muscarinic Activation of BK Channels Induces Membrane Oscillations in Glioma Cells and Leads to Inhibition of Cell MigrationThe Journal of Membrane Biology, 2000
- Evaluation of the Relative Cytotoxic Effects of Anticancer Agents in Serum‐supplemented versus Serum‐free Media Using a Tetrazolium Colorimetric AssayJapanese Journal of Cancer Research, 1996
- Transfection with bFGF sense and antisense cDNA resulting in modification of malignant glioma growthJournal of Neurosurgery, 1995
- Block of neuronal fast chloride channels by internal tetraethylammonium ions.The Journal of general physiology, 1994
- Voltage-dependent block of fast chloride channels from rat cortical neurons by external tetraethylammonium ion.The Journal of general physiology, 1992
- Role of ion channels in lymphocytesJournal of Clinical Immunology, 1991
- Cell Cycle Dependence of Chloride Permeability in Normal and Cystic Fibrosis LymphocytesScience, 1990