Local impermeant anions establish the neuronal chloride concentration

J Glykys, V Dzhala, K Egawa, T Balena, Y Saponjian, K V Kuchibhotla, B J Bacskai, K T Kahle, T Zeuthen, K J Staley

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159 Citations (Scopus)

Abstract

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.)
Volume343
Issue number6171
Pages (from-to)670-5
Number of pages6
ISSN0036-8075
DOIs
Publication statusPublished - 7 Feb 2014

Keywords

  • 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

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