Local impermeant anions establish the neuronal chloride concentration

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

Research output: Contribution to journalArticle

Abstract

Neuronal intracellular chloride concentration [Cl-]i is an important determinant of γ-aminobutyric acid type A (GABA A) receptor (GABAAR)-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 GABAAR signaling.

Original languageEnglish (US)
Pages (from-to)670-675
Number of pages6
JournalScience
Volume343
Issue number6171
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Anions
Chlorides
Cations
GABA-A Receptors
Aminobutyrates
Fluorophores
Brain
Glycoproteins
Ions
Membranes

ASJC Scopus subject areas

  • General

Cite this

Glykys, J., Dzhala, V., Egawa, K., Balena, T., Saponjian, Y., Kuchibhotla, K., ... Staley, K. J. (2014). Local impermeant anions establish the neuronal chloride concentration. Science, 343(6171), 670-675. https://doi.org/10.1126/science.1245423

Local impermeant anions establish the neuronal chloride concentration. / Glykys, J.; Dzhala, V.; Egawa, K.; Balena, T.; Saponjian, Y.; Kuchibhotla, Kishore; Bacskai, B. J.; Kahle, K. T.; Zeuthen, T.; Staley, K. J.

In: Science, Vol. 343, No. 6171, 01.01.2014, p. 670-675.

Research output: Contribution to journalArticle

Glykys, J, Dzhala, V, Egawa, K, Balena, T, Saponjian, Y, Kuchibhotla, K, Bacskai, BJ, Kahle, KT, Zeuthen, T & Staley, KJ 2014, 'Local impermeant anions establish the neuronal chloride concentration', Science, vol. 343, no. 6171, pp. 670-675. https://doi.org/10.1126/science.1245423
Glykys J, Dzhala V, Egawa K, Balena T, Saponjian Y, Kuchibhotla K et al. Local impermeant anions establish the neuronal chloride concentration. Science. 2014 Jan 1;343(6171):670-675. https://doi.org/10.1126/science.1245423
Glykys, J. ; Dzhala, V. ; Egawa, K. ; Balena, T. ; Saponjian, Y. ; Kuchibhotla, Kishore ; Bacskai, B. J. ; Kahle, K. T. ; Zeuthen, T. ; Staley, K. J. / Local impermeant anions establish the neuronal chloride concentration. In: Science. 2014 ; Vol. 343, No. 6171. pp. 670-675.
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