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

Weiwei Wang; Kouki K. Touhara; Keiko Weir; Bruce P. Bean; Roderick MacKinnon

doi:10.7554/eLife.15751

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

Weiwei Wang, Kouki K. Touhara, Keiko Weir, Bruce P. Bean, Roderick MacKinnon

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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 Gβɣ subunits bind cooperatively to open GIRK2, and that intracellular Na⁺ – which enters neurons during action potentials – further amplifies opening mostly by increasing Gβɣ affinity. A Na⁺ amplification function is characterized and used to estimate the concentration of Gβɣ subunits that appear in the membrane of mouse dopamine neurons when GABA_B receptors are stimulated. We conclude that GIRK2, through its dual responsiveness to Gβɣ and Na⁺, mediates a form of neuronal inhibition that is amplifiable in the setting of excess electrical activity.

Original language	English (US)
Article number	e15751
Journal	eLife
Volume	5
Issue number	April 2016
DOIs	https://doi.org/10.7554/eLife.15751
State	Published - Apr 13 2016
Externally published	Yes

ASJC Scopus subject areas

Neuroscience(all)
Immunology and Microbiology(all)
Biochemistry, Genetics and Molecular Biology(all)

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title = "Cooperative regulation by G proteins and Na+ of neuronal GIRK2 K+ channels",

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 Gβɣ subunits bind cooperatively to open GIRK2, and that intracellular Na+ – which enters neurons during action potentials – further amplifies opening mostly by increasing Gβɣ affinity. A Na+ amplification function is characterized and used to estimate the concentration of Gβɣ subunits that appear in the membrane of mouse dopamine neurons when GABAB receptors are stimulated. We conclude that GIRK2, through its dual responsiveness to Gβɣ and Na+, mediates a form of neuronal inhibition that is amplifiable in the setting of excess electrical activity.",

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AU - Touhara, Kouki K.

AU - Weir, Keiko

AU - Bean, Bruce P.

AU - MacKinnon, Roderick

N1 - Funding Information: National Institutes of Health NIHNS036855 Bruce P Bean, National Institutes of Health NIHGM43949 Roderick MacKinnon, Howard Hughes Medical Institute. Publisher Copyright: © Wang et al.

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

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