Functional modulation of GABAA receptors by cAMP-dependent protein phosphorylation

Stephen J. Moss, Trevor G. Smart, Craig D. Blackstone, Richard L. Huganir

Research output: Contribution to journalArticlepeer-review


γ-Aminobutyric acidA (GABAA) receptors are ligand-gated ion channels that mediate inhibitory synaptic transmission in the central nervous system. The role of protein phosphorylation in the modulation of GABAA receptor function was examined with cells transiently transfected with GABAA receptor subunits. GABAA receptors consisting of the α1 and β1 or the α1, β1, and γ2 subunits were directly phosphorylated on the β1 subunit by adenosine 3′,5′-monophosphate (cAMP)-dependent protein kinase (PKA). The phosphorylation decreased the amplitude of the GABA response of both receptor types and the extent of rapid desensitization of the GABAA receptor that consisted of the α1 and β1 subunits. Site-specific mutagenesis of the serine residue phosphorylated by PKA completely eliminated the PKA phosphorylation and modulation of the GABAA receptor. In primary embryonic rat neuronal cell cultures, a similar regulation of GABAA receptors by PKA was observed. These results demonstrate that the GABAA receptor is directly modulated by protein phosphorylation and suggest that neurotransmitters or neuropeptides that regulate intracellular cAMP levels may modulate the responses of neurons to GABA and consequently have profound effects on synaptic excitability.

Original languageEnglish (US)
Pages (from-to)661-665
Number of pages5
Issue number5070
StatePublished - 1992

ASJC Scopus subject areas

  • General

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