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

doi:10.1126/science.1245423

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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Abstract

Neuronal intracellular chloride concentration [Cl_-]_i is an important determinant of γ-aminobutyric acid type A (GABA _A) receptor (GABA_AR)-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_AR signaling.

Original language	English (US)
Pages (from-to)	670-675
Number of pages	6
Journal	Science
Volume	343
Issue number	6171
DOIs	https://doi.org/10.1126/science.1245423
State	Published - 2014
Externally published	Yes

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title = "Local impermeant anions establish the neuronal chloride concentration",

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.",

author = "J. Glykys and V. Dzhala and K. Egawa and T. Balena and Y. Saponjian and Kuchibhotla, {K. V.} and Bacskai, {B. J.} and Kahle, {K. T.} and T. Zeuthen and Staley, {K. J.}",

year = "2014",

doi = "10.1126/science.1245423",

language = "English (US)",

volume = "343",

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T1 - Local impermeant anions establish the neuronal chloride concentration

AU - Glykys, J.

AU - Dzhala, V.

AU - Egawa, K.

AU - Balena, T.

AU - Saponjian, Y.

AU - Kuchibhotla, K. V.

AU - Bacskai, B. J.

AU - Kahle, K. T.

AU - Zeuthen, T.

AU - Staley, K. J.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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VL - 343

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JO - Science

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Local impermeant anions establish the neuronal chloride concentration

Abstract

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