Local impermeant anions establish the neuronal chloride concentration

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 (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6171

ER -