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

ICMM Afdeling 8

111 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Science (New York, N.Y.)
Vol/bind	343
Udgave nummer	6171
Sider (fra-til)	670-5
Antal sider	6
ISSN	0036-8075
DOI	https://doi.org/10.1126/science.1245423
Status	Udgivet - 7 feb. 2014

Adgang til dokumentet

10.1126/science.1245423

Citationsformater

@article{02f1c964f01249b4bc4c4b0870ddf5f7,

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 (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.",

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",

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",

month = feb,

day = "7",

doi = "10.1126/science.1245423",

language = "English",

volume = "343",

pages = "670--5",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6171",

}

TY - JOUR

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 - 2014/2/7

Y1 - 2014/2/7

N2 - 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.

AB - 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.

KW - Animals

KW - Brain

KW - Cell Membrane Permeability

KW - Cell Polarity

KW - Chloride Channels

KW - Chlorides

KW - Cytoplasm

KW - Extracellular Matrix Proteins

KW - Glycoproteins

KW - Mice

KW - Mice, Transgenic

KW - Neurons

KW - Receptors, GABA-A

KW - Recombinant Fusion Proteins

KW - Signal Transduction

U2 - 10.1126/science.1245423

DO - 10.1126/science.1245423

M3 - Journal article

C2 - 24503855

SN - 0036-8075

VL - 343

SP - 670

EP - 675

JO - Science

JF - Science

IS - 6171

ER -

Local impermeant anions establish the neuronal chloride concentration

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater