Intracellular chloride concentration influences the GABAA receptor subunit composition

Nat Commun. 2012 Mar 13:3:738. doi: 10.1038/ncomms1744.

Abstract

GABA(A) receptors (GABA(A)Rs) exist as different subtype variants showing unique functional properties and defined spatio-temporal expression pattern. The molecular mechanisms underlying the developmental expression of different GABA(A)R are largely unknown. The intracellular concentration of chloride ([Cl(-)](i)), the main ion permeating through GABA(A)Rs, also undergoes considerable changes during maturation, being higher at early neuronal stages with respect to adult neurons. Here we investigate the possibility that [Cl(-)](i) could modulate the sequential expression of specific GABA(A)Rs subtypes in primary cerebellar neurons. We show that [Cl(-)](i) regulates the expression of α3-1 and δ-containing GABA(A) receptors, responsible for phasic and tonic inhibition, respectively. Our findings highlight the role of [Cl(-)](i) in tuning the strength of GABAergic responses by acting as an intracellular messenger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bumetanide / pharmacology
  • Carboxylic Acids / pharmacology
  • Cells, Cultured
  • Cerebellum / chemistry
  • Cerebellum / cytology
  • Chlorides / analysis
  • Chlorides / metabolism*
  • Indenes / pharmacology
  • Isoxazoles
  • K Cl- Cotransporters
  • Mice
  • Neurons / chemistry
  • Neurons / cytology
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Protein Subunits / metabolism
  • Pyridines / pharmacology
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, GABA-A / chemistry*
  • Receptors, GABA-A / metabolism*
  • Symporters / genetics
  • Symporters / metabolism
  • Zolpidem
  • gamma-Aminobutyric Acid / metabolism

Substances

  • ((dihydroindenyl)oxy)alkanoic acid
  • Carboxylic Acids
  • Chlorides
  • Indenes
  • Isoxazoles
  • Protein Subunits
  • Pyridines
  • RNA, Small Interfering
  • Receptors, GABA-A
  • Symporters
  • Bumetanide
  • gamma-Aminobutyric Acid
  • Zolpidem
  • gaboxadol