Local impermeant anions establish the neuronal chloride concentration
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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.
|Journal||Science (New York, N.Y.)|
|Number of pages||6|
|Publication status||Published - 7 Feb 2014|
- 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