The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 heterotetramers

Kouki K. Touhara, Weiwei Wang, Roderick Mackinnon

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 Gbg 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 Gbg, suggesting that the GIRK1 subunit functions like a GIRK4 subunit with Na+ permanently bound.

Original languageEnglish (US)
Article numbere15750
JournaleLife
Volume5
Issue numberApril 2016
DOIs
StatePublished - Apr 13 2016
Externally publishedYes

Fingerprint

GTP-Binding Proteins
G Protein-Coupled Inwardly-Rectifying Potassium Channels
GTP-Binding Protein gamma Subunits
GTP-Binding Protein beta Subunits
Chemical activation
Inwardly Rectifying Potassium Channel
Pacemakers
Lipid bilayers
Lipid Bilayers
Carrier Proteins
Heart Rate
Binding Sites
Lipids
Proteins
G-protein Beta gamma

ASJC Scopus subject areas

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

Cite this

The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 heterotetramers. / Touhara, Kouki K.; Wang, Weiwei; Mackinnon, Roderick.

In: eLife, Vol. 5, No. April 2016, e15750, 13.04.2016.

Research output: Contribution to journalArticle

Touhara, Kouki K. ; Wang, Weiwei ; Mackinnon, Roderick. / The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 heterotetramers. In: eLife. 2016 ; Vol. 5, No. April 2016.
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