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Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells.

Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. Research Abstract Details 

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  • Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. Abstract Text:

    Voltage-dependent large-conductance Ca(2+)-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 [Ca(2+)](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.

    Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. Publishing Authors By Initials

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    PUBMED ID PMID:

    MEDLINE DATE:

    Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: Journal of neuroscience research

    VOLUME: 78

    Page Numbers: 224-34

    Journal Abbreviation: J. Neurosci. Res.

    ISSN: 0360-4012

    DAY: 15

    MONTH: Oct

    YEAR: 2004

    Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7600111

    Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. Keywords Mesh Terms:

    KEYWORDS: Tetraethylammonium

    MESH TERMS: pharmacology

    Chemical & Substance for Abstract: Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. Information

    Substance Name: Tetraethylammonium

    Registry Number: 66-40-0

    Grant and Affiliation Information for Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells.

    AFFILIATION: Department of Neurobiology, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NINDS

    GRANT: R01-NS36692

    ACRONYM: NS

    MEDLINETA: J Neurosci Res

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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