cAMP-independent decrease of ATP-sensitive K+ channel activity by GLP-1 in rat pancreatic β-cells

2000 ◽  
Vol 440 (4) ◽  
pp. 566-572 ◽  
Author(s):  
Sechiko Suga ◽  
Takahiro Kanno ◽  
Yoshiji Ogawa ◽  
Teruko Takeo ◽  
Noritaka Kamimura ◽  
...  
Keyword(s):  
K Channel ◽  
Channel Activity ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic β-cells

1998 ◽  
Vol 274 (1) ◽  
pp. E38-E44 ◽  
Author(s):  
Eri Mukai ◽  
Hitoshi Ishida ◽  
Seika Kato ◽  
Yoshiyuki Tsuura ◽  
Shimpei Fujimoto ◽  
...  
Keyword(s):  
Metabolic Inhibition ◽  
K Channel ◽  
High Dose ◽  
Dependent Manner ◽  
Channel Activity ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Patch Clamp Technique ◽  
Channel Inhibition ◽  
Dose Dependent

The effect of metabolic inhibition on the blocking of β-cell ATP-sensitive K+ channels (KATP channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of KATP channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 μM) of ATP applied in the inside-out mode, KATP channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose-dependent and complete KATP channel inhibition under 10 μM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATP channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K+ channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, KATPchannel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic β-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.

scholarly journals Intracellular Ca2+ Modulation of ATP-Sensitive K+ Channel Activity in Acetylcholine-Induced Activation of Rat Pancreatic β-Cells

Endocrinology ◽  
2002 ◽  
Vol 143 (2) ◽  
pp. 569-576 ◽  
Author(s):  
Kyoko Nakano ◽  
Sechiko Suga ◽  
Teruko Takeo ◽  
Yoshiji Ogawa ◽  
Toshihiro Suda ◽  
...  
Keyword(s):  
K Channel ◽  
Channel Activity ◽  
Β Cells ◽  
Pancreatic Β Cells

ATP Sensitivity of the ATP-Sensitive K+Channel in Intact and Permeabilized Pancreatic β-Cells

Diabetes ◽  
2006 ◽  
Vol 55 (9) ◽  
pp. 2446-2454 ◽  
Author(s):  
Andrei I. Tarasov ◽  
Christophe A.J. Girard ◽  
Frances M. Ashcroft
Keyword(s):  
K Channel ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress

2009 ◽  
Author(s):  
Belinda Gier ◽  
Peter Krippeit-Drews ◽  
Tatiana Sheiko ◽  
Lydia Aguilar-Bryan ◽  
Joseph Bryan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Katp Channel ◽  
Channel Activity ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Gregory M Martin ◽  
Craig Yoshioka ◽  
Emily A Rex ◽  
Jonathan F Fay ◽  
Qing Xie ◽  
...  
Keyword(s):  
Symmetry Axis ◽  
Transmembrane Domain ◽  
Katp Channels ◽  
Structural Basis ◽  
Channel Activity ◽  
Membrane Excitability ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Binding Domains ◽  
Channel Assembly

KATP channels are metabolic sensors that couple cell energetics to membrane excitability. In pancreatic β-cells, channels formed by SUR1 and Kir6.2 regulate insulin secretion and are the targets of antidiabetic sulfonylureas. Here, we used cryo-EM to elucidate structural basis of channel assembly and gating. The structure, determined in the presence of ATP and the sulfonylurea glibenclamide, at ~6 Å resolution reveals a closed Kir6.2 tetrameric core with four peripheral SUR1s each anchored to a Kir6.2 by its N-terminal transmembrane domain (TMD0). Intricate interactions between TMD0, the loop following TMD0, and Kir6.2 near the proposed PIP2 binding site, and where ATP density is observed, suggest SUR1 may contribute to ATP and PIP2 binding to enhance Kir6.2 sensitivity to both. The SUR1-ABC core is found in an unusual inward-facing conformation whereby the two nucleotide binding domains are misaligned along a two-fold symmetry axis, revealing a possible mechanism by which glibenclamide inhibits channel activity.

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