GIRK channel activation involves a local rearrangement of a preformed G protein channel complex.
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.
Riven
Inbal
I
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel 76100.
Iwanir
Shachar
S
Reuveny
Eitan
E
D002460:Cell Line; D031541:Fluorescence Resonance Energy Transfer; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000737:chemistry / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020836:Protein Structure, Quaternary / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins