Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMP-dependent protein kinase

Nat Neurosci. 1998 May;1(1):23-8. doi: 10.1038/223.


Activation of cAMP-dependent protein kinase (PKA) can enhance or reduce the function of neuronal GABAA receptors, the major sites of fast synaptic inhibition in the brain. This differential regulation depends on PKA-induced phosphorylation of adjacent conserved sites in the receptor beta subunits. Phosphorylation of beta 3 subunit-containing receptors at S408 and S409 enhanced the GABA-activated response, whereas selectively mutating S408 to alanine converted the potentiation into an inhibition, comparable to that of beta 1 subunits, which are phosphorylated solely on S409. These distinct modes of regulation were interconvertible between beta 1 and beta 3 subunits and depended upon the presence of S408 in either subunit. In contrast, beta 2 subunit-containing receptors were not phosphorylated or affected by PKA. Differential regulation by PKA of postsynaptic GABAA receptors containing different beta subunits may have profound effects on neuronal excitability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enzyme Activation / physiology
  • Humans
  • Isomerism
  • Mice
  • Mutation / physiology
  • Patch-Clamp Techniques
  • Phosphorylation
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Receptors, GABA-A / physiology
  • Transfection
  • gamma-Aminobutyric Acid / pharmacology


  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases