scholarly journals G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward

2016 ◽  
Vol 40 (4) ◽  
pp. 857-864 ◽  
Author(s):  
Megan E. Tipps ◽  
Jonathan D. Raybuck ◽  
Laura B. Kozell ◽  
K. Matthew Lattal ◽  
Kari J. Buck
Keyword(s):  
Potassium Channel ◽  
G Protein ◽  
Knock Out ◽  
Inwardly Rectifying Potassium Channel ◽  
Knock Out Mice ◽  
Inwardly Rectifying

scholarly journals Structural basis for the ethanol action on G-protein–activated inwardly rectifying potassium channel 1 revealed by NMR spectroscopy

2018 ◽  
Vol 115 (15) ◽  
pp. 3858-3863 ◽  
Author(s):  
Yuki Toyama ◽  
Hanaho Kano ◽  
Yoko Mase ◽  
Mariko Yokogawa ◽  
Masanori Osawa ◽  
...  
Keyword(s):  
Nervous System ◽  
Nmr Spectroscopy ◽  
Potassium Channel ◽  
G Protein ◽  
Structural Basis ◽  
Signaling Proteins ◽  
Inwardly Rectifying Potassium Channel ◽  
Wide Range ◽  
Inwardly Rectifying ◽  
Human Nervous System

Ethanol consumption leads to a wide range of pharmacological effects by acting on the signaling proteins in the human nervous system, such as ion channels. Despite its familiarity and biological importance, very little is known about the molecular mechanisms underlying the ethanol action, due to extremely weak binding affinity and the dynamic nature of the ethanol interaction. In this research, we focused on the primary in vivo target of ethanol, G-protein–activated inwardly rectifying potassium channel (GIRK), which is responsible for the ethanol-induced analgesia. By utilizing solution NMR spectroscopy, we characterized the changes in the structure and dynamics of GIRK induced by ethanol binding. We demonstrated here that ethanol binds to GIRK with an apparent dissociation constant of 1.0 M and that the actual physiological binding site of ethanol is located on the cavity formed between the neighboring cytoplasmic regions of the GIRK tetramer. From the methyl-based NMR relaxation analyses, we revealed that ethanol activates GIRK by shifting the conformational equilibrium processes, which are responsible for the gating of GIRK, to stabilize an open conformation of the cytoplasmic ion gate. We suggest that the dynamic molecular mechanism of the ethanol-induced activation of GIRK represents a general model of the ethanol action on signaling proteins in the human nervous system.

scholarly journals The biochemical study of the novel splicing variant of G protein-gated inwardly rectifying potassium channel (Kir 3.1)

1999 ◽  
Vol 79 ◽  
pp. 90
Author(s):  
Shigeto Matsumoto ◽  
Ken-Icirou Morishige ◽  
Hiroshi Hibino ◽  
Atsushi Inanobe ◽  
Yoshiyuki Horio ◽  
...  
Keyword(s):  
Potassium Channel ◽  
G Protein ◽  
Biochemical Study ◽  
The Novel ◽  
Splicing Variant ◽  
Inwardly Rectifying Potassium Channel ◽  
Inwardly Rectifying
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