Acid-sensing ion channels in malignant gliomas

Bakhrom K. Berdiev, Jiazeng Xia, Lee Anne McLean, James M. Markert, G. Yancey Gillespie, Timothy B. Mapstone, Anjaparavanda P. Naren, Biljana Jovov, James K. Bubien, Hong Long Ji, Catherine M. Fuller, Kevin L. Kirk, Dale J. Benos

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Abstract

High grade glioma cells derived from patient biopsies express an amiloride-sensitive sodium conductance that has properties attributed to the human brain sodium channel family, also known as acid-sensing ion channels (ASICs). This amiloride-sensitive conductance was not detected in cells obtained from normal brain tissue or low grade or benign tumors. Differential gene profiling data showed that ASIC1 and ASIC2 mRNA were present in normal and low grade tumor cells. Although ASIC1 was present in all of the high grade glial cells examined, ASIC2 mRNA was detected in less than half. The main purpose of our work was to examine the molecular mechanisms that may underlie the constitutively activated sodium currents present in high grade glioma cells. Our results show that 1) gain-of-function mutations of ASIC1 were not present in a number of freshly resected and cultured high grade gliomas, 2) syntaxin 1A inhibited ASIC currents only when ASIC1 and ASIC2 were co-expressed, and 3) the inhibition of ASIC currents by syntaxin 1A had an absolute requirement for either γ- or δ-hENaC. Transfection of cultured cells originally derived from high grade gliomas (U87-MG and SK-MG1) with ASIC2 abolished basal amiloride-sensitive sodium conductance; this inhibition was reversed by dialysis of the cell interior with Munc-18, a syntaxin-binding protein that typically blocks the interaction of syntaxin with other proteins. Thus, syntaxin 1A cannot inhibit Na+ permeability in the absence of adequate plasma membrane ASIC2 expression, accounting for the observed functional expression of amiloride-sensitive currents in high grade glioma cells.

Original languageEnglish
Pages (from-to)15023-15034
Number of pages12
JournalJournal of Biological Chemistry
Volume278
Issue number17
DOIs
Publication statusPublished - Apr 25 2003
Externally publishedYes

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Acid Sensing Ion Channels
Amiloride
Syntaxin 1
Glioma
Qa-SNARE Proteins
Sodium
Tumors
Brain
Cells
Messenger RNA
Dialysis
Biopsy
Sodium Channels
Cell membranes
Carrier Proteins
Genes
Tissue
Neuroglia
Transfection
Cultured Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Berdiev, B. K., Xia, J., McLean, L. A., Markert, J. M., Gillespie, G. Y., Mapstone, T. B., ... Benos, D. J. (2003). Acid-sensing ion channels in malignant gliomas. Journal of Biological Chemistry, 278(17), 15023-15034. https://doi.org/10.1074/jbc.M300991200

Acid-sensing ion channels in malignant gliomas. / Berdiev, Bakhrom K.; Xia, Jiazeng; McLean, Lee Anne; Markert, James M.; Gillespie, G. Yancey; Mapstone, Timothy B.; Naren, Anjaparavanda P.; Jovov, Biljana; Bubien, James K.; Ji, Hong Long; Fuller, Catherine M.; Kirk, Kevin L.; Benos, Dale J.

In: Journal of Biological Chemistry, Vol. 278, No. 17, 25.04.2003, p. 15023-15034.

Research output: Contribution to journalArticle

Berdiev, BK, Xia, J, McLean, LA, Markert, JM, Gillespie, GY, Mapstone, TB, Naren, AP, Jovov, B, Bubien, JK, Ji, HL, Fuller, CM, Kirk, KL & Benos, DJ 2003, 'Acid-sensing ion channels in malignant gliomas', Journal of Biological Chemistry, vol. 278, no. 17, pp. 15023-15034. https://doi.org/10.1074/jbc.M300991200
Berdiev BK, Xia J, McLean LA, Markert JM, Gillespie GY, Mapstone TB et al. Acid-sensing ion channels in malignant gliomas. Journal of Biological Chemistry. 2003 Apr 25;278(17):15023-15034. https://doi.org/10.1074/jbc.M300991200
Berdiev, Bakhrom K. ; Xia, Jiazeng ; McLean, Lee Anne ; Markert, James M. ; Gillespie, G. Yancey ; Mapstone, Timothy B. ; Naren, Anjaparavanda P. ; Jovov, Biljana ; Bubien, James K. ; Ji, Hong Long ; Fuller, Catherine M. ; Kirk, Kevin L. ; Benos, Dale J. / Acid-sensing ion channels in malignant gliomas. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 17. pp. 15023-15034.
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