Endogenous ClC-2 channels contribute to mammalian cell volume homeostasis

R. M. Roman, R. L. Smith, A. P. Feranchak, G. H. Clayton, J. G. Fitz

Research output: Contribution to journalArticlepeer-review


The molecular identity of the membrane Cl- channels responsible for cell volume homeostasis has not been defined. Since previous studies have shown that Xenopus-expressed ClC-2 channels activate during hypotonic exposure, our purpose was to evaluate whether endogenous mammalian ClC-2 channels contribute to volume-sensitive changes in membrane Cl- permeability. A cDNA closely homologous with rat brain ClC-2 was isolated from a model liver cell line that demonstrates swelling-activated currents typical of most mammalian cell types. Abundant cellular expression of ClC-2 mRNA and membrane localization of ClC-2 protein was shown by in situ hybridization and immunocytochemistry. Intracellular delivery of antibodies to the cytoplasmic amino-terminal region of ClC-2 thought to be important for channel gating nearly abolished Cl- current activation by volume increases or exposure to ATP. lntracellular injection of ClC-2 antibodies also prevented recovery of cell volume following swelling. The characteristics of volume-and ATP-stimulated unitary currents include a slope conductance that averaged 7.6 pS in symmetrical Cl- containing solutions, reversal near ECl, and a permeability ratio of NO3- > Cl- > aspartate. These studies provide the first direct evidence that native mammalian ClC-2 channel proteins contribute to membrane Cl- permeability and volume homeostasis, and may have important implications for other cell types in light of the near ubiquitous expression of ClC-2.

Original languageEnglish (US)
Pages (from-to)A1024
JournalFASEB Journal
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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