1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics

The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers

  1. Kouki K Touhara
  2. Weiwei Wang
  3. Roderick MacKinnon  Is a corresponding author
  1. Howard Hughes Medical Institute, Rockefeller University, United States
https://doi.org/10.7554/eLife.15750
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  1. Kouki K Touhara
  2. Weiwei Wang
  3. Roderick MacKinnon
(2016)
The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers
eLife 5:e15750.
https://doi.org/10.7554/eLife.15750
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Abstract

G protein gated inward rectifier potassium (GIRK) channels are gated by direct binding of G protein beta-gamma subunits (Gβγ), signaling lipids, and intracellular Na+. In cardiac pacemaker cells, hetero-tetramer GIRK1/4 channels and homo-tetramer GIRK4 channels play a central role in parasympathetic slowing of heart rate. It is known that the Na+ binding site of the GIRK1 subunit is defective, but the functional difference between GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers remains unclear. Here, using purified proteins and the lipid bilayer system, we characterize Gβγ and Na+ regulation of GIRK1/4 hetero-tetramers and GIRK4 homo-tetramers. We find in GIRK4 homo-tetramers that Na+ binding increases Gβγ affinity and thereby increases the GIRK4 responsiveness to G protein stimulation. GIRK1/4 hetero-tetramers are not activated by Na+, but rather are in a permanent state of high responsiveness to Gβγ, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with Na+ permanently bound.

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Author details

  1. Kouki K Touhara

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Weiwei Wang

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Roderick MacKinnon

    Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, United States
    For correspondence
    mackinn@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2016, Touhara et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kouki K Touhara
  2. Weiwei Wang
  3. Roderick MacKinnon
(2016)
The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers
eLife 5:e15750.
https://doi.org/10.7554/eLife.15750

Share this article

https://doi.org/10.7554/eLife.15750

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