Local impermeant anions establish the neuronal chloride concentration

Research output: Contribution to journalJournal articleResearchpeer-review

  • J Glykys
  • V Dzhala
  • K Egawa
  • T Balena
  • Y Saponjian
  • K V Kuchibhotla
  • B J Bacskai
  • K T Kahle
  • Zeuthen, Thomas
  • K J Staley
Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of γ-aminobutyric acid type A (GABA(A)) receptor (GABA(A)R)-mediated inhibition and cytoplasmic volume regulation. Equilibrative cation-chloride cotransporters (CCCs) move Cl(-) across the membrane, but accumulating evidence suggests factors other than the bulk concentrations of transported ions determine [Cl(-)](i). Measurement of [Cl(-)](i) in murine brain slice preparations expressing the transgenic fluorophore Clomeleon demonstrated that cytoplasmic impermeant anions ([A](i)) and polyanionic extracellular matrix glycoproteins ([A](o)) constrain the local [Cl(-)]. CCC inhibition had modest effects on [Cl(-)](i) and neuronal volume, but substantial changes were produced by alterations of the balance between [A](i) and [A](o). Therefore, CCCs are important elements of Cl(-) homeostasis, but local impermeant anions determine the homeostatic set point for [Cl(-)], and hence, neuronal volume and the polarity of local GABA(A)R signaling.
Original languageEnglish
JournalScience (New York, N.Y.)
Issue number6171
Pages (from-to)670-5
Number of pages6
Publication statusPublished - 7 Feb 2014

    Research areas

  • Animals, Brain, Cell Membrane Permeability, Cell Polarity, Chloride Channels, Chlorides, Cytoplasm, Extracellular Matrix Proteins, Glycoproteins, Mice, Mice, Transgenic, Neurons, Receptors, GABA-A, Recombinant Fusion Proteins, Signal Transduction

ID: 109651930