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 journalArticlepeer-review

36 Scopus citations


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.

Original languageEnglish (US)
Article numbere15751
Issue numberApril 2016
StatePublished - Apr 13 2016
Externally publishedYes

ASJC Scopus subject areas

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


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