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Elife. 2016 Apr 13;5. pii: e15751. doi: 10.7554/eLife.15751.

Cooperative regulation by G proteins and Na(+) of neuronal GIRK2 K(+) channels.

Author information

1
Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, United States.
2
Department of Neurobiology, Harvard Medical School, Boston, 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.

KEYWORDS:

G protein; G protein gated potassium channel; Ni-NTA lipid; biochemistry; biophysics; dopaminergic neuron; mouse; planar lipid bilayer; sodium activation; structural biology

Comment in

PMID:
27074662
PMCID:
PMC4866826
DOI:
10.7554/eLife.15751
[Indexed for MEDLINE]
Free PMC Article

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