 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, July 2, 2003, 23(13):5572-5582
Previous Article | Next Article
Expression of Voltage-Gated Chloride Channels in Human Glioma Cells
M. L. Olsen, S. Schade, S. A. Lyons, M. D. Amaral, andH. Sontheimer Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294
Voltage-gated chloride channels have recently been implicated as being important for cell proliferation and invasive cell migration of primary brain tumors cells. In the present study we provide several lines of evidence that glioma Cl– currents are primarily mediated by ClC-2 and ClC-3, two genes that belong to the ClC superfamily. Transcripts for ClC-2 thru ClC-7 were detected in a human glioma cell line by PCR, whereas only ClC-2, ClC-3, and ClC-5 protein could be identified by Western blot. Prominent ClC-2, -3, and -5 channel expression was also detected in acute patient biopsies from low- and high-grade malignant gliomas. Immunogold electron microscopic studies as well as digital confocal imaging localized a portion of these ClC channels to the plasma membrane. Whole-cell patch-clamp recordings show the presence of two pharmacologically and biophysically distinct Cl– currents that could be specifically reduced by 48 hr exposure of cells to channel-specific antisense oligonucleotides. ClC-3 antisense selectively and significantly reduced the expression of outwardly rectifying current with pronounced voltage-dependent inactivation. Such currents were sensitive to DIDS (200–500 µM) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (165 µM). ClC-2 antisense significantly reduced expression of inwardly rectifying currents, which were potentiated by hyperpolarizing prepulses and inhibited by Cd2+ (200–500 µm). Currents that were mediated by ClC-5 could not be demonstrated. We suggest that ClC-2 and ClC-3 channels are specifically upregulated in glioma membranes and endow glioma cells with an enhanced ability to transport Cl–. This may in turn facilitate rapid changes in cell size and shape as cells divide or invade through tortuous extracellular brain spaces.
Key words: ClC channel; brain tumor; patch clamp; antisense knockdown; cell migration; cell proliferation
Received Dec. 12, 2002; revised Apr. 23, 2003; accepted Apr. 23, 2003.
This article has been cited by other articles:
C. W. Habela, M. L. Olsen, and H. Sontheimer
ClC3 Is a Critical Regulator of the Cell Cycle in Normal and Malignant Glial Cells
J. Neurosci., September 10, 2008; 28(37): 9205 - 9217.
[Abstract] [Full Text] [PDF]
H. Sontheimer
An Unexpected Role for Ion Channels in Brain Tumor Metastasis
Experimental Biology and Medicine, July 1, 2008; 233(7): 779 - 791.
[Abstract] [Full Text] [PDF]
S. B. Ross, C. M. Fuller, J. K. Bubien, and D. J. Benos
Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells
Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1181 - C1185.
[Abstract] [Full Text] [PDF]
K. S. Suh, J. M. Crutchley, A. Koochek, A. Ryscavage, K. Bhat, T. Tanaka, A. Oshima, P. Fitzgerald, and S. H. Yuspa
Reciprocal Modifications of CLIC4 in Tumor Epithelium and Stroma Mark Malignant Progression of Multiple Human Cancers
Clin. Cancer Res., January 1, 2007; 13(1): 121 - 131.
[Abstract] [Full Text] [PDF]
G. Cheng, M.-J. Kim, G. Jia, and D. K. Agrawal
Involvement of chloride channels in IGF-I-induced proliferation of porcine arterial smooth muscle cells
Cardiovasc Res, January 1, 2007; 73(1): 198 - 207.
[Abstract] [Full Text] [PDF]
J. Hegermann, J. Overbeck, and H. Schrempf
In vivo monitoring of the potassium channel KcsA in Streptomyces lividans hyphae using immuno-electron microscopy and energy-filtering transmission electron microscopy.
Microbiology, September 1, 2006; 152(Pt 9): 2831 - 2841.
[Abstract] [Full Text] [PDF]
E. E. Benarroch
Neuron-Astrocyte Interactions: Partnership for Normal Function and Disease in the Central Nervous System
Mayo Clin. Proc., October 1, 2005; 80(10): 1326 - 1338.
[Abstract] [PDF]
N. J. Ernest, A. K. Weaver, L. B. Van Duyn, and H. W. Sontheimer
Relative contribution of chloride channels and transporters to regulatory volume decrease in human glioma cells
Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1451 - C1460.
[Abstract] [Full Text] [PDF]
J.-G. Zhou, J.-L. Ren, Q.-y. Qiu, H. He, and Y.-Y. Guan
Regulation of Intracellular Cl- Concentration through Volume-regulated ClC-3 Chloride Channels in A10 Vascular Smooth Muscle Cells
J. Biol. Chem., February 25, 2005; 280(8): 7301 - 7308.
[Abstract] [Full Text] [PDF]
K. S. Suh, M. Mutoh, M. Gerdes, J. M. Crutchley, T. Mutoh, L. E. Edwards, R. A. Dumont, P. Sodha, C. Cheng, A. Glick,, et al.
Antisense Suppression of the Chloride Intracellular Channel Family Induces Apoptosis, Enhances Tumor Necrosis Factor {alpha}-Induced Apoptosis, and Inhibits Tumor Growth
Cancer Res., January 15, 2005; 65(2): 562 - 571.
[Abstract] [Full Text] [PDF]
S. Yamamoto-Mizuma, G.-X. Wang, L. L. Liu, K. Schegg, W. J. Hatton, D. Duan, T. L. B. Horowitz, F. S. Lamb, and J. R. Hume
Altered properties of volume-sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3-/- mice
J. Physiol., June 1, 2004; 557(2): 439 - 456.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|