Cooperative regulation by G proteins and Na+ of neuronal GIRK2 K+ channels
- Howard Hughes Medical Institute, Rockefeller University, United States
Abstract
G protein gated inward rectifier K+ (GIRK) channels open and thereby silence cellular electrical activity when inhibitory G protein coupled receptors (GPCRs) are stimulated. Here we describe an assay to measure neuronal GIRK2 activity as a function of membrane-anchored G protein concentration. Using this assay we show that four Gβγ subunits bind cooperatively to open GIRK2, and that intracellular Na+ - which enters neurons during action potentials - further amplifies opening mostly by increasing Gβγ affinity. A Na+ amplification function is characterized and used to estimate the concentration of Gβγ subunits that appear in the membrane of mouse dopamine neurons when GABAB receptors are stimulated. We conclude that GIRK2, through its dual responsiveness to Gβγ and Na+, mediates a form of neuronal inhibition that is amplifiable in the setting of excess electrical activity.
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Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to a protocol approved by the institutional animal care and use committee (IACUC) of Harvard Medical School (Protocol #02538-R98).
Copyright
© 2016, Wang 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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Cooperative regulation by G proteins and Na+ of neuronal GIRK2 K+ channels
eLife 5:e15751.
https://doi.org/10.7554/eLife.15751
Further reading
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- Biochemistry and Chemical Biology
- Structural Biology and Molecular Biophysics
Experiments on artificial membranes are revealing many details about the workings of a family of potassium ion channels called GIRK channels.
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- Biochemistry and Chemical Biology
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