Local impermeant anions establish the neuronal chloride concentration
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Local impermeant anions establish the neuronal chloride concentration. / Glykys, J; Dzhala, V; Egawa, K; Balena, T; Saponjian, Y; Kuchibhotla, K V; Bacskai, B J; Kahle, K T; Zeuthen, T; Staley, K J.
In: Science (New York, N.Y.), Vol. 343, No. 6171, 07.02.2014, p. 670-5.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 343
SP - 670
EP - 675
JO - Science
JF - Science
SN - 0036-8075
IS - 6171
ER -
ID: 109651930