Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.
Activation of G protein-gated K+ channels by G protein-coupled receptors contributes to parasympathetic regulation of heart rate in the atrium and inhibitory postsynaptic potentials in the peripheral and central nervous system. Having found that G beta gamma activates the cloned GIRK1 channel, we now report evidence for direct binding of G beta gamma to both the N-terminal hydrophilic domain and amino acids 273-462 of the C-terminal domain of GIRK1. These direct interactions are physiologically important because synthetic peptides derived from either domain reduce the G beta gamma binding as well as the G beta gamma activation of the channel. Moreover, the N-terminal domain may also bind trimeric G alpha beta gamma, raising the possibility that physical association of G protein-coupled receptors, G proteins, and K+ channels partially accounts for their compartmentalization and hence rapid and specific channel activation by receptors.
Huang
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CL
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco 94143-0724, USA.
Slesinger
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Casey
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PJ
Jan
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Jan
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D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D015153:Blotting, Western; D011232:Chemical Precipitation; D004594:Electrophysiology; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000502:physiology*; D018014:Gene Transfer Techniques; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018411:Spodoptera / Q000378:metabolism; D014982:Xenopus laevis
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D010446:Peptide Fragments; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011976:Receptors, Muscarinic; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins