Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells.
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.
Ross
Sandra B
SB
Dept. Physiology and Biophysics, Univ. of Alabama at Birmingham, 1918 University Blvd., MCLM 704, Birmingham, AL 35294-0005, USA. benos@uab.edu
Fuller
Catherine M
CM
Bubien
James K
JK
Benos
Dale J
DJ
D000584:Amiloride / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009997:Osmotic Pressure; D010455:Peptides; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; D000584:Amiloride; D012964:Sodium