GIRK channel activation involves a local rearrangement of a preformed G protein channel complex

Neuron. 2006 Sep 7;51(5):561-73. doi: 10.1016/j.neuron.2006.08.017.


G protein-coupled signaling is one of the major mechanisms for controlling cellular excitability. One of the main targets for this control at postsynaptic membranes is the G protein-coupled potassium channels (GIRK/Kir3), which generate slow inhibitory postsynaptic potentials following the activation of Pertussis toxin-sensitive G protein-coupled receptors. Using total internal reflection fluorescence (TIRF) microscopy combined with fluorescence resonance energy transfer (FRET), in intact cells, we provide evidence for the existence of a trimeric G protein-channel complex at rest. We show that activation of the channel via the receptor induces a local conformational switch of the G protein to induce channel opening. The presence of such a complex thus provides the means for a precise temporal and highly selective activation of the channel, which is required for fine tuning of neuronal excitability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Fluorescence Resonance Energy Transfer
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / chemistry
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology*
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / physiology*
  • Humans
  • Membrane Potentials / physiology
  • Microscopy, Fluorescence
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Protein Structure, Quaternary / physiology*
  • Signal Transduction / physiology*


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Proteins