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Local impermeant anions establish the neuronal chloride concentration.


ABSTRACT: Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of ?-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.

SUBMITTER: Glykys J 

PROVIDER: S-EPMC4220679 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Local impermeant anions establish the neuronal chloride concentration.

Glykys J J   Dzhala V V   Egawa K K   Balena T T   Saponjian Y Y   Kuchibhotla K V KV   Bacskai B J BJ   Kahle K T KT   Zeuthen T T   Staley K J KJ  

Science (New York, N.Y.) 20140201 6171


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 fluoropho  ...[more]

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