![]()
|
|
||||||||
J. Biol. Chem., Vol. 278, Issue 17, 15023-15034, April 25, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,
,
§,
¶,
,
**,
,
,
,
,
, and

From the Departments of 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
Physiology and Biophysics and
¶ Surgery, University of Alabama at Birmingham, Birmingham,
Alabama 35294 and the
Department of Neurosurgery, Emory
University, Atlanta, Georgia 30322
- or
-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.

To whom correspondence should be addressed: Dept. of Physiology
and Biophysics, The University of Alabama at Birmingham, 1918 University Blvd., MCLM 704, Birmingham, AL 35294-0005. Tel.:
205-934-6220; Fax: 205-934-2377; E-mail:
benos@physiology.uab.edu.
This article has been cited by other articles:
![]() |
S. C. Grifoni, S. E. McKey, and H. A. Drummond Hsc70 regulates cell surface ASIC2 expression and vascular smooth muscle cell migration Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2022 - H2030. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Fuller and D. J. Benos Putting the brakes on vascular smooth muscle cell migration Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H1987 - H1988. [Full Text] [PDF] |
||||
![]() |
H. A. Drummond, N. L. Jernigan, and S. C. Grifoni Sensing Tension: Epithelial Sodium Channel/Acid-Sensing Ion Channel Proteins in Cardiovascular Homeostasis Hypertension, May 1, 2008; 51(5): 1265 - 1271. [Full Text] [PDF] |
||||
![]() |
K. P. Gannon, L. G. VanLandingham, N. L. Jernigan, S. C. Grifoni, G. Hamilton, and H. A. Drummond Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1793 - H1803. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. A. Drummond, S. C. Grifoni, and N. L. Jernigan A New Trick for an Old Dogma: ENaC Proteins as Mechanotransducers in Vascular Smooth Muscle Physiology, February 1, 2008; 23(1): 23 - 31. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-H. Cho and C. C. Askwith Presynaptic Release Probability Is Increased in Hippocampal Neurons From ASIC1 Knockout Mice J Neurophysiol, February 1, 2008; 99(2): 426 - 441. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. H. Vila-Carriles, Z.-H. Zhou, J. K. Bubien, C. M. Fuller, and D. J. Benos Participation of the Chaperone Hsc70 in the Trafficking and Functional Expression of ASIC2 in Glioma Cells J. Biol. Chem., November 23, 2007; 282(47): 34381 - 34391. [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] |
||||
![]() |
R. H. Meltzer, N. Kapoor, Y. J. Qadri, S. J. Anderson, C. M. Fuller, and D. J. Benos Heteromeric Assembly of Acid-sensitive Ion Channel and Epithelial Sodium Channel Subunits J. Biol. Chem., August 31, 2007; 282(35): 25548 - 25559. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Su, Q. Li, K. Shrestha, E. Cormet-Boyaka, L. Chen, P. R. Smith, E. J. Sorscher, D. J. Benos, S. Matalon, and H.-L. Ji Interregulation of Proton-gated Na+ Channel 3 and Cystic Fibrosis Transmembrane Conductance Regulator J. Biol. Chem., December 1, 2006; 281(48): 36960 - 36968. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. H. Vila-Carriles, G. G. Kovacs, B. Jovov, Z.-H. Zhou, A. K. Pahwa, G. Colby, O. Esimai, G. Y. Gillespie, T. B. Mapstone, J. M. Markert, et al. Surface Expression of ASIC2 Inhibits the Amiloride-sensitive Current and Migration of Glioma Cells J. Biol. Chem., July 14, 2006; 281(28): 19220 - 19232. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. S. Adams, K. R. Robinson, T. Fukumoto, S. Yuan, R. C. Albertson, P. Yelick, L. Kuo, M. McSweeney, and M. Levin Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates Development, May 1, 2006; 133(9): 1657 - 1671. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. P. Price, R. J. Thompson, J. O. Eshcol, J. A. Wemmie, and C. J. Benson Stomatin Modulates Gating of Acid-sensing Ion Channels J. Biol. Chem., December 17, 2004; 279(51): 53886 - 53891. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. K. Bubien, H.-L. Ji, G. Y. Gillespie, C. M. Fuller, J. M. Markert, T. B. Mapstone, and D. J. Benos Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1 Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1282 - C1291. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-L. Ji and D. J. Benos Degenerin Sites Mediate Proton Activation of {delta}{beta}{gamma}-Epithelial Sodium Channel J. Biol. Chem., June 25, 2004; 279(26): 26939 - 26947. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. K. Berdiev, B. Jovov, W. C. Tucker, A. P. Naren, C. M. Fuller, E. R. Chapman, and D. J. Benos ENaC subunit-subunit interactions and inhibition by syntaxin 1A Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1100 - F1106. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. C. Askwith, J. A. Wemmie, M. P. Price, T. Rokhlina, and M. J. Welsh Acid-sensing Ion Channel 2 (ASIC2) Modulates ASIC1 H+-activated Currents in Hippocampal Neurons J. Biol. Chem., April 30, 2004; 279(18): 18296 - 18305. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |