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

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


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
Issue number6171
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • General


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