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Am J Physiol Cell Physiol 293: C1181-C1185, 2007. First published July 5, 2007; doi:10.1152/ajpcell.00066.2007
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REPORT

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells

Sandra B. Ross, Catherine M. Fuller, James K. Bubien, and Dale J. Benos

Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 16 February 2007 ; accepted in final form 28 June 2007

ABSTRACT

Despite intensive research, brain tumors remain among the most difficult type of malignancies to treat, due largely to their diffusely invasive nature and the associated difficulty of adequate surgical resection. To migrate through the brain parenchyma and to proliferate, glioma cells must be capable of significant changes in shape and volume. We have previously reported that glioma cells express an amiloride- and psalmotoxin-sensitive cation conductance that is not found in normal human astrocytes. In the present study, we investigated the potential role of this ion channel to mediate regulatory volume increase in glioma cells. We found that the ability of the cells to volume regulate subsequent to cell shrinkage by hyperosmolar solutions was abolished by both amiloride and psalmotoxin 1. This toxin is thought to be a specific peptide inhibitor of acid-sensing ion channel (ASIC1), a member of the Deg/ENaC superfamily of cation channels. We have previously shown this toxin to be an effective blocker of the glioma cation conductance. Our data suggest that one potential role for this conductance may be to restore cell volume during the cell's progression thorough the cell cycle and while the tumor cell migrates within the interstices of the brain.

brain tumor; sodium; epithelial sodium channel; acid-sensing ion channel; psalmotoxin



Address for reprint requests and other correspondence: D. Benos, Dept. Physiology and Biophysics, Univ. of Alabama at Birmingham, 1918 University Blvd., MCLM 704, Birmingham, AL 35294-0005 (e-mail: benos{at}uab.edu)




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