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ATP sensitive potassium channel

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https://www.readbyqxmd.com/read/29128812/pharmacological-evidence-for-the-involvement-of-adenosine-triphosphate-sensitive-potassium-channels-in-chloroquine-induced-itch-in-mice
#1
Sattar Ostadhadi, Arash Foroutan, Nazgol-Sadat Haddadi, Abbas Norouzi-Javidan, Majid Momeny, Ghazaleh Zarrinrad, Seyed Hamid Ghaffari, Ahmad-Reza Dehpour
BACKGROUND: Chloroquine (CQ) evokes itch in human and scratching behavior in rodents through a histamine-independent pathway. Chloroquine directly excites peripheral sensory neurons which convey itch signals to the central nervous system. It has been revealed that ATP-sensitive potassium channels (KATP channels) are important in regulating neuronal excitability. Thus, we aimed to investigate the involvement of KATP channels in CQ-induced itch which may also reveal a linkage between metabolic state of cells and itch...
June 3, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29119680/nicorandil-regulates-the-macrophage-skewing-and-ameliorates-myofibroblasts-by-inhibition-of-rhoa-rho-kinase-signalling-in-infarcted-rats
#2
Tsung-Ming Lee, Shinn-Zong Lin, Nen-Chung Chang
We have demonstrated that ATP-sensitive potassium (KATP ) channel agonists attenuated fibrosis; however, the mechanism remained unclear. Since RhoA has been identified as a mediator of cardiac fibrosis, we sought to determine whether the anti-fibrotic effects of KATP channel agonists were mediated via regulating macrophage phenotype and fibroblast differentiation by a RhoA/RhoA-kinase-dependent pathway. Wistar male rats after induction of myocardial infarction were randomized to either vehicle, nicorandil, an antagonist of KATP channel glibenclamide, an antagonist of ROCK fasudil, or a combination of nicorandil and glibenclamide or fasudil and glibenclamide starting 24 hrs after infarction...
November 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29115470/dimethylation-of-histone-3-lysine-9-is-sensitive-to-the-epileptic-activity-and-affects-the-transcriptional-regulation-of-the-potassium-channel-kcnj10-gene-in-epileptic-rats
#3
Shao-Ping Zhang, Man Zhang, Hong Tao, Yan Luo, Tao He, Chun-Hui Wang, Xiao-Cheng Li, Ling Chen, Lin-Na Zhang, Tao Sun, Qi-Kuan Hu
Potassium channels can be affected by epileptic seizures and serve a crucial role in the pathophysiology of epilepsy. Dimethylation of histone 3 lysine 9 (H3K9me2) and its enzyme euchromatic histone‑lysine N‑methyltransferase 2 (G9a) are the major epigenetic modulators and are associated with gene silencing. Insight into whether H3K9me2 and G9a can respond to epileptic seizures and regulate expression of genes encoding potassium channels is the main purpose of the present study. A total of 16 subtypes of potassium channel genes in pilocarpine‑modelled epileptic rats were screened by reverse transcription‑quantitative polymerase chain reaction, and it was determined that the expression ATP‑sensitive inward rectifier potassium channel 10 (Kcnj10) increased in hippocampus and insular cortex, while the expression of most of the other subtypes decreased...
November 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29114841/effect-of-cromakalim-prodrug-1-cklp1-on-aqueous-humor-dynamics-and-feasibility-of-combination-therapy-with-existing-ocular-hypotensive-agents
#4
Uttio Roy Chowdhury, Tommy A Rinkoski, Cindy K Bahler, J Cameron Millar, Jacques A Bertrand, Bradley H Holman, Joseph M Sherwood, Darryl R Overby, Kristen L Stoltz, Peter I Dosa, Michael P Fautsch
Purpose: Cromakalim prodrug 1 (CKLP1) is a water-soluble ATP-sensitive potassium channel opener that has shown ocular hypotensive properties in ex vivo and in vivo experimental models. To determine its mechanism of action, we assessed the effect of CKLP1 on aqueous humor dynamics and in combination therapy with existing ocular hypotensive agents. Methods: Outflow facility was assessed in C57BL/6 mice by ex vivo eye perfusions and by in vivo constant flow infusion following CKLP1 treatment...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29094209/comparison-of-the-protective-effects-of-direct-ischemic-preconditioning-and-remote-ischemic-preconditioning-in-a-rabbit-model-of-transient-spinal-cord-ischemia
#5
Takehiko Fukui, Kazuyoshi Ishida, Yoichi Mizukami, Kiyotaka Shiramoto, Hidenori Harada, Atsuo Yamashita, Satoshi Yamashita, Mishiya Matsumoto
INTRODUCTION: This study aimed to determine the relative potency of direct ischemic preconditioning (DIPC) and remote ischemic preconditioning (RIPC) for protection against ischemic spinal cord injury in rabbits and to explore the mechanisms involved. METHODS: In experiment 1, we compared the neurological and histopathological outcomes of DIPC, kidney RIPC, and limb RIPC. The DIPC and kidney RIPC groups received two cycles of 5-min occlusion/15-min reperfusion of the abdominal aorta and left renal artery, respectively...
November 1, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/29076887/the-use-of-levosimendan-in-cardiac-surgery-an-update-after-the-levo-cts-cheetah-and-licorn-trials-in-the-light-of-clinical-practice
#6
Fabio Guarracino, Matthias Heringlake, Bernard Cholley, Dominique Bettex, Stefaan Bouchez, Vladimir V Lomivorotov, Angela Rajek, Matti Kivikko, Piero Pollesello
Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener which exerts sustained hemodynamic, symptomatic and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past fifteen years, levosimendan has been widely used in clinical practice, and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, three randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH and LEVO-CTS) have been published reporting on the peri-operative use of levosimendan in patients with compromised cardiac ventricular function...
October 30, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29058186/methods-for-characterizing-disease-associated-atp-sensitive-potassium-channel-mutations
#7
Balamurugan Kandasamy, Show-Ling Shyng
The ATP-sensitive potassium (KATP) channel formed by the inwardly rectifying potassium channel Kir6.2 and the sulfonylurea receptor 1 (SUR1) plays a key role in regulating insulin secretion. Genetic mutations in KCNJ11 or ABCC8 which encode Kir6.2 and SUR1 respectively are major causes of insulin secretion disorders: those causing loss of channel function lead to congenital hyperinsulinism, whereas those causing gain of channel function result in neonatal diabetes and in some cases developmental delay, epilepsy, and neonatal diabetes, referred to as the DEND syndrome...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29058183/probing-subunits-interactions-in-katp-channels-using-photo-crosslinking-via-genetically-encoded-p-azido-l-phenylalanine
#8
Prasanna Devaraneni, Emily A Rex, Show-Ling Shyng
Potassium channels are multimeric protein complexes regulated by diverse physiological and pharmacological ligands. The key to understanding mechanisms of channel regulation is the ability to detect structural changes associated with ligand binding. While high-resolution structural methods such as X-ray crystallography and single-particle cryo-electron microscopy offer direct visualization of channel structures, these methods do have limitations and may not be suitable for the question of interest. In this chapter, we describe the use of a photo-cross-linker unnatural amino acid, p-azido-L-phenylalanine, to probe interactions between two proteins, the sulfonylurea receptor 1 and the inwardly rectifying potassium channel Kir6...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29058181/monitoring-changes-in-the-abundance-of-endogenously-expressed-atp-sensitive-potassium-katp-channels-in-the-plasma-membrane-using-surface-biotinylation
#9
Jing-Syuna Ruan, Pei-Chun Chen
The conductance of KATP channel activity can be regulated by gating and/or surface expression. Gating analysis is usually performed by electrophysiological recording. Analysis of surface KATP channel expression levels requires cell fractionation, protein separation, and quantification. Cell fractionation involves time-consuming high-speed centrifugation steps and skilled techniques for taking out specific layers. Moreover, contamination of intracellular membranes can confound results. Although commercial kits have been developed to make it easier for scientists, qualities of these kits vary which can give rise to variable results...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29056256/glibenclamide-inhibits-nlrp3-inflammasome-mediated-il-1%C3%AE-secretion-in-human-trophoblasts
#10
Kazuhiro Tamura, Gen Ishikawa, Mikihiro Yoshie, Wakana Ohneda, Akihito Nakai, Toshiyuki Takeshita, Eiichi Tachikawa
Infection-associated pregnancy complications cause premature delivery. Caspase-1 is involved in the maturation of interleukin (IL)-1β, which is activated by the NLRP3 inflammasome. To characterize the significance of the NLRP3 inflammasome pathway in the placenta, the effects of activators and inhibitors on NLRP3-related molecules were examined using isolated primary trophoblasts. Caspase-1 and IL-1β mRNA expression was markedly increased in response to lipopolysaccharide (LPS), a toll-like receptor (TLR)4 ligand...
October 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29052402/-effect-of-qibai-pingfei-capsule-medicated-serum-on-protein-expressions-of-katp-channel-in-pulmonary-arterial-smooth-muscle-cells-via-nitric-oxide
#11
Jie Zhu, Ze-Geng Li, Bao-Qin Wang, Xiang-Li Tong, Qing-He Peng
To investigate the ATP-sensitive potassium channel (KATP channel) protein expressions during different periods under hypoxia condition and explore the effect of Qibai Pingfei capsule medicated serum (hereinafter referred to as QBPF) on the correlation between the protein expressions of KATP channel and nitric oxide in rat pulmonary arterial smooth muscle cells(PASMCs). Qibai Pingfei capsules were given to SD rats via continuous gavage for 10 days to obtain QBPF. Primary rats PASMCs were cultured by the direct adherent culture method...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29042208/antiallodynic-activity-of-leflunomide-is-partially-inhibited-by-naltrexone-and-glibenclamide-and-associated-with-reduced-production-of-tnf-%C3%AE-and-cxcl-1
#12
Ana Mercy S Brito, Adriana M Godin, Paulo Sérgio A Augusto, Raquel R Menezes, Ivo S F Melo, Marcela G M B Dutra, Sarah O A M Costa, Franciele A Goulart, Felipe F Rodrigues, Marcela Ísis Morais, Renes R Machado, Márcio M Coelho
Leflunomide, an immunosuppressive drug approved for the treatment of patients with rheumatoid arthritis, exhibits many mechanisms which may affect the nociceptive processing. Therefore, the present study aimed to evaluate the effect induced by leflunomide on the mechanical allodynia in models of inflammatory and neuropathic pain in mice and investigate mechanisms mediating such effects. Per os (p.o.) administration of leflunomide (25, 50 or 100mg/kg) inhibited the inflammatory edema and mechanical allodynia induced by intraplantar carrageenan...
October 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29034901/generation-of-a-kcnj11-homozygous-knockout-human-embryonic-stem-cell-line-wae001-a-12-using-crispr-cas9
#13
Fang Yuan, Dongsheng Guo, Ge Gao, Yanli Liu, Yingying Xu, Yuhang Wu, Fan Yang, Xinrong Ke, Keyu Lai, Liangqing Hong, Yin-Xiong Li
The ATP-sensitive potassium channel is an octameric complex, and one of its subunits, namely Kir6.2, is encoded by the KCNJ11 gene. Mutations in KCNJ11 result in hyperinsulinism or diabetes mellitus, associated with abnormal insulin secretion. Here, using CRISPR/Cas9 editing, we established a homozygous mutant KCNJ11 cell line, WAe001-A-12, which was generated by a 62-bp deletion in the coding sequence of the human embryonic stem cell line H1. It was confirmed that this deletion in the KCNJ11 gene did not affect the protein expression levels of key pluripotent factors...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29022263/cardiac-ischemia-reperfusion-injury-the-beneficial-effects-of-exercise
#14
Juliana Pereira Borges, Karine da Silva Verdoorn
Cardiac ischemia reperfusion injury (IRI) occurs when the myocardium is revascularized after an episode of limited or absent blood supply. Many changes, including free radical production, calcium overload, protease activation, altered membrane lipids and leukocyte activation, contribute to IRI-induced myocardium damage. Aerobic exercise is the only countermeasure against IRI that can be sustained on a regular basis in clinical practice. Interestingly, both short-term (3-5 days) and long-term (several weeks) exercise increase myocardial tolerance, reduce infarct size area and arrhythmias induced by IRI...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28978764/calcium-dynamics-control-k-atp-channel-mediated-bursting-in-substantia-nigra-dopamine-neurons-a-combined-experimental-and-modeling-study
#15
Christopher J Knowlton, Sylvie Kutterer, Jochen Roeper, Carmen C Canavier
Burst firing in medial substantia nigra dopamine (mSN DA) neurons has been selectively linked to novelty-induced exploration behavior in mice. Burst firing in mSN DA neurons, in contrast to lateral SN DA neurons, requires functional ATP-sensitive potassium channels (K-ATP) both in vitro and in vivo. However, the precise role of K-ATP channels in promoting burst firing is un-known. We show experimentally that L-type calcium channel activity in mSN DA neurons en-hances open probability of K-ATP channels. We then generated a mathematical model to study the role of Ca(2+) dynamics driving K-ATP channel function in mSN DA neurons during bursting...
October 4, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28977592/cftr-influences-beta-cell-function-and-insulin-secretion-through-non-cell-autonomous-exocrine-derived-factors
#16
Xingshen Sun, Yaling Yi, Weiliang Xie, Bo Liang, Michael C Winter, Nan He, Xiaoming Liu, Meihui Luo, Yu Yang, Katie Larson Ode, Aliye Uc, Andrew W Norris, John F Engelhardt
Although β-cell dysfunction in cystic fibrosis (CF) leads to diabetes, the mechanism by which the cystic fibrosis transmembrane conductance regulator (CFTR) channel influences islet insulin secretion remains debated. We investigated the CFTR-dependent islet-autonomous mechanisms affecting insulin secretion by using islets isolated from CFTR knockout ferrets. Total insulin content was lower in CF as compared with wild-type (WT) islets. Furthermore, glucose-stimulated insulin secretion (GSIS) was impaired in perifused neonatal CF islets, with reduced first, second, and amplifying phase secretion...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28971696/hydrogen-sulfide-ameliorated-l-name-induced-hypertensive-heart-disease-by-the-akt-enos-no-pathway
#17
Sheng Jin, Xu Teng, Lin Xiao, Hongmei Xue, Qi Guo, Xiaocui Duan, Yuhong Chen, Yuming Wu
Reductions in hydrogen sulfide (H2S) production have been implicated in the pathogenesis of hypertension; however, no studies have examined the functional role of hydrogen sulfide in hypertensive heart disease. We hypothesized that the endogenous production of hydrogen sulfide would be reduced and exogenous hydrogen sulfide would ameliorate cardiac dysfunction in N(ω)-nitro- L-arginine methyl ester ( L-NAME)-induced hypertensive rats. Therefore, this study investigated the cardioprotective effects of hydrogen sulfide on L-NAME-induced hypertensive heart disease and explored potential mechanisms...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28968949/diazoxide-prevents-h2o2-induced-chondrocyte-apoptosis-and-cartilage-degeneration-in-a-rat-model-of-osteoarthritis-by-reducing-endoplasmic-reticulum-stress
#18
YunTao Gu, Jian Chen, ZhuLong Meng, JiangLing Yao, WanYu Ge, KeWei Chen, ShaoWen Cheng, Jian Fu, Lei Peng, YingZheng Zhao
Osteoarthritis (OA) is a common disease affecting elderly individuals. Its incidence rises sharply with age, and chondrocyte apoptosis plays a vital role in its pathogenesis. Diazoxide opens mitochondrial ATP-sensitive potassium (mitoKATP) channels and exerts multiple pharmacological effects, including reductions in blood pressure and blood sugar levels. It also exerts anti-apoptotic activities, but the cellular and molecular mechanisms by which diazoxide inhibits chondrocyte apoptosis are unknown, as is whether apoptosis is related to endoplasmic reticulum stress (ERS)...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28967705/deciphering-structure-activity-relationships-in-a-series-of-2-2-dimethylchromans-acting-as-inhibitors-of-insulin-release-and-smooth-muscle-relaxants
#19
Bernard Pirotte, Xavier Florence, Eric Goffin, Philippe Lebrun
4,6-Disubstituted 2,2-dimethylchromans are reported as pharmacologically active compounds that mainly target the ATP-sensitive potassium channels. The present study is an attempt to characterize the impact of the nature of substituents introduced at the 4- and 6-positions of 2,2-dimethylchromans on their capacities to inhibit insulin release from pancreatic β-cells or to relax vascular smooth muscle cells, both biological responses that are supposed to reflect interaction with specific ion channels. From the core structure 4-amino-2,2-dimethylchroman, a progressive increase in the steric hindrance of the chemical functionalities introduced at the 4-position (amino, formamido, acetamido, arylureido/thioureido) and at the 6-position (amino, formamido, acetamido, alkoxycarbonylamino) led to a progressive magnification of the inhibitory effect on the insulin release process and, to a lesser extent, of the vasorelaxant activity...
October 2, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28964153/mechanism-underlying-impaired-cardiac-pacemaking-rhythm-during-ischemia-a-simulation-study
#20
Xiangyun Bai, Kuanquan Wang, Yongfeng Yuan, Qince Li, Halina Dobrzynski, Mark R Boyett, Jules C Hancox, Henggui Zhang
Ischemia in the heart impairs function of the cardiac pacemaker, the sinoatrial node (SAN). However, the ionic mechanisms underlying the ischemia-induced dysfunction of the SAN remain elusive. In order to investigate the ionic mechanisms by which ischemia causes SAN dysfunction, action potential models of rabbit SAN and atrial cells were modified to incorporate extant experimental data of ischemia-induced changes to membrane ion channels and intracellular ion homeostasis. The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-atrium...
September 2017: Chaos
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