Multiple roles of protein kinases in the modulation of gamma-aminobutyric acid(A) receptor function and cell surface expression

Pharmacol Ther. 2002 Apr-May;94(1-2):113-22. doi: 10.1016/s0163-7258(02)00175-4.

Abstract

gamma-Aminobutyric acid(A) (GABA(A)) receptors are ligand-gated ion channels that mediate the majority of fast synaptic inhibition in the brain and that are also important drug targets for benzodiazepines, barbiturates, and neurosteriods. These receptors are pentameric hetero-oligomers that can be assembled from 7 subunit classes with multiple members: alpha(1-6), beta(1-3), gamma(1-3), delta, epsilon, theta, and pi. Most receptor subtypes in the brain, however, are believed to be composed of alpha-, beta-, and gamma-subunits. Modifications of GABA(A) receptor function are continually implicated in a range of pathologies, including epilepsy, anxiety, insomnia, and substance abuse. Moreover, changes in the efficacy of synaptic inhibition mediated by GABA(A) receptors are believed to be play central roles in certain forms of synaptic plasticity, including rebound potentiation in the cerebellum, and hippocampal long-term potentiation. Given the critical role that GABA(A) receptors play as mediators of synaptic transmission, it is of fundamental importance to understand the endogenous mechanisms used by neurones to control the function of these receptors. This review will focus on the dynamic regulation of GABA(A) receptor phosphorylation state and channel function as mechanisms involved in determining the efficacy of synaptic inhibition. In addition, the possible role of GABA(A) receptor phosphorylation in controlling receptor internalization and recycling will also be explored.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation
  • Humans
  • Phosphorylation
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Receptors, GABA-A / physiology*
  • Signal Transduction

Substances

  • Receptors, GABA-A
  • Protein Kinases