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.
| Original language | English |
|---|---|
| Journal | Science (New York, N.Y.) |
| Volume | 343 |
| Issue number | 6171 |
| Pages (from-to) | 670-5 |
| Number of pages | 6 |
| ISSN | 0036-8075 |
| DOIs | |
| Publication status | Published - 7 Feb 2014 |
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