scholarly journals Heteromerization of alkaline-sensitive two-pore domain potassium channels

2021 ◽  
Author(s):  
Lamyaa Khoubza ◽  
Eun-Jin Kim ◽  
Franck C Chatelain ◽  
Sylvain Feliciangeli ◽  
Dawon Kang ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Chromosomal Region ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Transcriptomic Data ◽  
Human Genes ◽  
K2p Channels ◽  
Genes Encoding ◽  
Pore Domain ◽  
Different Tissues

Two-pore domain (K2P) potassium channels are active as dimers. They produce inhibitory currents regulated by a variety of stimuli. Among them, TALK1, TALK2 and TASK2 form a subfamily of structurally related K2P channels stimulated by extracellular alkalosis. The human genes encoding them are clustered on chromosomal region 6p21. They are expressed in different tissues including the pancreas. By analyzing single cell transcriptomic data, we show that these channels are co-expressed in insulin-secreting pancreatic β cells. By different approaches we show that they form functional heterodimers. Heteromerization of TALK2 with TALK1 or with TASK2 endorses TALK2 with sensitivity to extracellular alkalosis in the physiological range. The association of TASK2 with TALK1 and TALK2 increases their unitary conductance. These results provide a new example of heteromerization in the K2P channel family expanding the range of their potential physiological and pathophysiological roles.

scholarly journals Characterization of potassium channels in pancreatic β cells from ob /ob mice

FEBS Letters ◽  
1990 ◽  
Vol 266 (1-2) ◽  
pp. 105-108 ◽  
Author(s):  
Manuel Kukuljan ◽  
Min Yi Li ◽  
Illani Atwater
Keyword(s):  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Activation of ATP-sensitive potassium channels in rat pancreatic β-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway

2008 ◽  
Vol 198 (3) ◽  
pp. 533-540 ◽  
Author(s):  
Yu-Feng Zhao ◽  
Jianming Pei ◽  
Chen Chen
Keyword(s):  
Linoleic Acid ◽  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Intracellular Metabolites ◽  
Cell Dysfunction ◽  
Triacsin C ◽  
Glucose Stimulated Insulin Secretion ◽  
G Protein Coupled

ATP-sensitive potassium channels (KATP channels) determine the excitability of pancreatic β-cells and importantly regulate glucose-stimulated insulin secretion (GSIS). Long-chain free fatty acids (FFAs) decrease GSIS after long-term exposure to β-cells, but the effects of exogenous FFAs on KATP channels are not yet well clarified. In this study, the effects of linoleic acid (LA) on membrane potential (MP) and KATP channels were observed in primary cultured rat pancreatic β-cells. LA (20 μM) induced hyperpolarization of MP and opening of KATP channels, which was totally reversed and inhibited by tolbutamide, a KATP channel blocker. Inhibition of LA metabolism by acyl-CoA synthetase inhibitor, triacsin C (10 μM), partially inhibited LA-induced opening of KATP channels by 64%. The non-FFA G protein-coupled receptor (GPR) 40 agonist, GW9508 (40 μM), induced an opening of KATP channels, which was similar to that induced by LA under triacsin C treatment. Blockade of protein kinases A and C did not influence the opening of KATP channels induced by LA and GW9508, indicating that these two protein kinase pathways are not involved in the action of LA on KATP channels. The present study demonstrates that LA induces hyperpolarization of MP by activating KATP channels via both intracellular metabolites and activation of GPR40. It indicates that not only intracellular metabolites of FFAs but also GPR40-mediated pathways take part in the inhibition of GSIS and β-cell dysfunction induced by FFAs.

6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-Dioxide Derivatives Potently and Selectively Activate ATP Sensitive Potassium Channels of Pancreatic β-Cells

2002 ◽  
Vol 45 (19) ◽  
pp. 4171-4187 ◽  
Author(s):  
Flemming E. Nielsen ◽  
Thora B. Bodvarsdottir ◽  
Anne Worsaae ◽  
Peter MacKay ◽  
Carsten E. Stidsen ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Propofol inhibits stromatoxin-1-sensitive voltage-dependent K+ channels in pancreatic β-cells and enhances insulin secretion

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8157 ◽  
Author(s):  
Munenori Kusunoki ◽  
Mikio Hayashi ◽  
Tomohiro Shoji ◽  
Takeo Uba ◽  
Hiromasa Tanaka ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Energy Metabolism ◽  
Glycemic Control ◽  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Kv Channels ◽  
Voltage Dependent ◽  
Cellular Oxygen ◽  
Low Glucose

Background Proper glycemic control is an important goal of critical care medicine, including perioperative patient care that can influence patients’ prognosis. Insulin secretion from pancreatic β-cells is generally assumed to play a critical role in glycemic control in response to an elevated blood glucose concentration. Many animal and human studies have demonstrated that perioperative drugs, including volatile anesthetics, have an impact on glucose-stimulated insulin secretion (GSIS). However, the effects of the intravenous anesthetic propofol on glucose metabolism and insulin sensitivity are largely unknown at present. Methods The effect of propofol on insulin secretion under low glucose or high glucose was examined in mouse MIN6 cells, rat INS-1 cells, and mouse pancreatic β-cells/islets. Cellular oxygen or energy metabolism was measured by Extracellular Flux Analyzer. Expression of glucose transporter 2 (GLUT2), potassium channels, and insulin mRNA was assessed by qRT-PCR. Protein expression of voltage-dependent potassium channels (Kv2) was also assessed by immunoblot. Propofol’s effects on potassium channels including stromatoxin-1-sensitive Kv channels and cellular oxygen and energy metabolisms were also examined. Results We showed that propofol, at clinically relevant doses, facilitates insulin secretion under low glucose conditions and GSIS in MIN6, INS-1 cells, and pancreatic β-cells/islets. Propofol did not affect intracellular ATP or ADP concentrations and cellular oxygen or energy metabolism. The mRNA expression of GLUT2 and channels including the voltage-dependent calcium channels Cav1.2, Kir6.2, and SUR1 subunit of KATP, and Kv2 were not affected by glucose or propofol. Finally, we demonstrated that propofol specifically blocks Kv currents in β-cells, resulting in insulin secretion in the presence of glucose. Conclusions Our data support the hypothesis that glucose induces membrane depolarization at the distal site, leading to KATP channel closure, and that the closure of Kv channels by propofol depolarization in β-cells enhances Ca2+ entry, leading to insulin secretion. Because its activity is dependent on GSIS, propofol and its derivatives are potential compounds that enhance and initiate β-cell electrical activity.

scholarly journals Structures of the human two-pore domain potassium channels TREK-1 and TREK-2

2014 ◽  
Vol 70 (a1) ◽  
pp. C1489-C1489
Author(s):  
Ashley Pike ◽  
Yin Dong ◽  
Alexandra Mackenzie ◽  
Conor McClenaghan ◽  
Shubhashish Mukhopadhyay ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Channel Gating ◽  
Resting Membrane Potential ◽  
Transmembrane Helices ◽  
Ion Conductance ◽  
K2p Channels ◽  
Extracellular Stimuli ◽  
Structural Mechanisms ◽  
Pore Domain ◽  
Pore Lining

TREK-1/2 are members of the mechano-gated subfamily of two-pore (K2P) domain potassium channels leaking K+ out of the cell and contributing to the resting membrane potential. In contrast to the classical tetrameric potassium channels, K2P channels are dimeric with an atypical architecture and the structural mechanisms underlying their channel gating are poorly understood. Here we present the crystal structures of human TREK-1 and TREK-2 at resolutions of 2.7 and 3.4Å which provide insights into the basis of intracellular and extracellular gating in this unique family of ion channels. We have solved the structure of TREK-2 in two distinct conformations differing in the orientation of the pore-lining transmembrane helices. The C-terminal M4 helix is hinged at a conserved glycine residue so that it adopts one of two distinct orientations. The M4 helix is either kinked towards the membrane, packing against the M2 inner helix of the adjacent subunit ("M4 up") or straightens and interacts with the M2/M3 helices from the same subunit ("M4 down"). In the M4 down state, a hydrophobic lateral opening runs perpendicular to the ion conductance pathway between M2 and M4 and links the inner vestibule to the membrane-exposed face of the channel. Transition between the "M4 down" and "M4 up" conformations may play a role in channel activation and gating. Cocrystallisation with a TREK-1/2 channel inhibitor promotes the "M4 down" state. The structure of TREK-1 exhibits an "M4-up" conformation but is unusual in that the selectivity filter is significantly distorted with only two correctly-formed potassium sites. The structure also reveals a divalent ion binding site between the extracellular cap and the pore domain loop. The TREK-1 structure illustrates how changes at an extracellular site can affect the pore structure. The structures will be described in detail along with their implications for channel gating in response to intracellular and extracellular stimuli.

Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells

Nature ◽  
1984 ◽  
Vol 312 (5993) ◽  
pp. 446-448 ◽  
Author(s):  
Frances M. Ashcroft ◽  
Donna E. Harrison ◽  
Stephen J. H. Ashcroft
Keyword(s):  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Isolated Rat

scholarly journals Inhibition of voltage-dependent potassium channels mediates cAMP-potentiated insulin secretion in rat pancreatic β cells

Islets ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 11-18 ◽  
Author(s):  
Yunfeng Liu ◽  
Xiangqin Zhong ◽  
Yaqin Ding ◽  
Lele Ren ◽  
Tao Bai ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Voltage Dependent

scholarly journals Negative Influence by the Force: Mechanically Induced Hyperpolarization via K2P Background Potassium Channels

2021 ◽  
Vol 22 (16) ◽  
pp. 9062
Author(s):  
Miklós Lengyel ◽  
Péter Enyedi ◽  
Gábor Czirják
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Potassium Channels ◽  
Cell Types ◽  
Negative Influence ◽  
Phospholipid Bilayer ◽  
Cellular Functions ◽  
K2p Channels ◽  
K Current ◽  
Pore Domain

The two-pore domain K2P subunits form background (leak) potassium channels, which are characterized by constitutive, although not necessarily constant activity, at all membrane potential values. Among the fifteen pore-forming K2P subunits encoded by the KCNK genes, the three members of the TREK subfamily, TREK-1, TREK-2, and TRAAK are mechanosensitive ion channels. Mechanically induced opening of these channels generally results in outward K+ current under physiological conditions, with consequent hyperpolarization and inhibition of membrane potential-dependent cellular functions. In the past decade, great advances have been made in the investigation of the molecular determinants of mechanosensation, and members of the TREK subfamily have emerged among the best-understood examples of mammalian ion channels directly influenced by the tension of the phospholipid bilayer. In parallel, the crucial contribution of mechano-gated TREK channels to the regulation of membrane potential in several cell types has been reported. In this review, we summarize the general principles underlying the mechanical activation of K2P channels, and focus on the physiological roles of mechanically induced hyperpolarization.

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