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ATP sensitive potassium channel

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https://www.readbyqxmd.com/read/28101177/analysis-on-mechanism-of-atp-sensitive-k-channel-opener-natakalim-improving-congestive-heart-failure-after-myocardial-infarction
#1
Feng Jin
The action mechanism of natakalim, a novel ATP-sensitive potassium channel opener, was studied in ameliorating the congestive heart failure (CHF) after myocardial infarction. A total of 25 healthy Wistar male rats (age, 10 weeks; average weight, 300 g) were selected, and the CHF models after acute myocardial infarction (AMI) were prepared by ligation of left anterior descending branch. They were randomly divided into the sham operation group, the model group and the groups of 1, 3 and 9 mg/kg/day natakalims...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28092267/cryo-em-structure-of-the-atp-sensitive-potassium-channel-illuminates-mechanisms-of-assembly-and-gating
#2
Gregory M Martin, Craig Yoshioka, Emily A Rex, Jonathan F Fay, Qing Xie, Matthew R Whorton, James Z Chen, Show-Ling Shyng
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 ~6Å 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)...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28076808/spatiotemporal-modeling-of-triggering-and-amplifying-pathways-in-glp-1-secreting-intestinal-l-cells
#3
Alessia Tagliavini, Morten Gram Pedersen
Glucagon-like peptide 1 (GLP-1) is secreted by intestinal L-cells, and augments glucose-induced insulin secretion, thus playing an important role in glucose control. The stimulus-secretion pathway in L-cells is still incompletely understood and a topic of debate. It is known that GLP-1 secreting cells can sense glucose to promote electrical activity either by the electrogenic sodium-glucose cotransporter SGLT1, or by closure of ATP-sensitive potassium channels after glucose metabolism. Glucose also has an effect on GLP-1 secretion downstream of electrical activity...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28065754/mechanisms-involved-in-antinociception-induced-by-a-polysulfated-fraction-from-seaweed-gracilaria-cornea-in-the-temporomandibular-joint-of-rats
#4
Chistiane Oliveira Coura, Hellíada Vasconcelos Chaves, Danielle Rocha do Val, Lorena Vasconcelos Vieira, Felipe Dantas Silveira, Fernanda Maxcynne Lino Dos Santos Lopes, Francisco Isaac Fernandes Gomes, Annyta Fernandes Frota, Ricardo Basto Souza, Juliana Trindade Clemente-Napimoga, Mirna Marques Bezerra, Norma Maria Barros Benevides
Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior...
January 5, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28054274/nicorandil-improves-post-fatigue-tension-in-slow-skeletal-muscle-fibers-by-modulating-glutathione-redox-state
#5
E Sánchez-Duarte, X Trujillo, C Cortés-Rojo, A Saavedra-Molina, G Camargo, L Hernández, M Huerta, R Montoya-Pérez
Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (KATP) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoKATP channels). K(+) channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study...
January 4, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28042862/hydrogen-sulfide-in-the-adipose-tissue-physiology-pathology-and-a-target-for-pharmacotherapy
#6
REVIEW
Jerzy Bełtowski, Anna Jamroz-Wiśniewska
Hydrogen sulfide (H₂S) is synthesized in the adipose tissue mainly by cystathionine γ-lyase (CSE). Several studies have demonstrated that H₂S is involved in adipogenesis, that is the differentiation of preadipocytes to adipocytes, most likely by inhibiting phosphodiesterases and increasing cyclic AMP concentration. The effect of H₂S on adipose tissue insulin sensitivity and glucose uptake is controversial. Some studies suggest that H₂S inhibits insulin-induced glucose uptake and that excess of H₂S contributes to adipose tissue insulin resistance in metabolic syndrome...
December 31, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28035625/effect-of-dexmedetomidine-on-cerebral-ischemia-reperfusion-rats-by-activating-mitochondrial-atp-sensitive-potassium-channel
#7
Feng Yuan, Hongguang Fu, Kai Sun, Shubiao Wu, Tieli Dong
The aim of the study reported here was to evaluate whether the mitochondrial ATP-sensitive potassium (mitoKATP) channel could participate in the effect of dexmedetomidine on cerebral ischemia-reperfusion (I/R) rats. Forty rats were randomly assigned into 5 groups: sham operation (S) group; cerebral I/R group; dexmedetomidine (D) group; 5-hydroxydecanoate (5-HD) group; 5-HD + D group. The cerebral I/R were produced by 2 h right middle cerebral artery occlusion followed by 24 h reperfusion. Dexmedetomidine (50μg/kg) was injected intraperitoneally before ischemia and after the onset of reperfusion...
December 29, 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28018462/a-novel-mutation-of-abcc8-gene-in-a-patient-with-diazoxide-unresponsive-congenital-hyperinsulinism
#8
Ji Sook Park, Hong-Jun Lee, Chan-Hoo Park
Congenital hyperinsulinism (CHI) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia. Hypoglycemia in CHI occurs secondary to the dysregulation of insulin secretion. CHI has been established as a genetic disorder of islet-cell hyperplasia, associated with a mutation of the ABCC8 or KCNJ11 genes, which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel (Kir6.2) subunit of the ATP-sensitive potassium channel, respectively...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/28003364/stromal-interaction-molecule-1-stim1-regulates-atp-sensitive-potassium-katp-and-store-operated-ca2-channels-in-min6-%C3%AE-cells
#9
Colin A Leech, Richard F Kopp, Heather A Nelson, Jyotirmoy Nandi, Michael W Roe
Stromal interaction molecule 1 (STIM1) regulates store-operated Ca(2+) entry (SOCE) and other ion channels, either as an endoplasmic reticulum (ER) Ca(2+) sensing protein or when present in the plasma membrane. However, the role of STIM1 in insulin-secreting β-cells is unresolved. We report that lowering expression of STIM1, the gene that encodes STIM1, in insulin-secreting MIN6 β-cells with RNA interference inhibits SOCE and ATP-sensitive K(+) (KATP) channel activation. The effects of STIM1 knockdown were reversed by transduction of MIN6 cells with an adenovirus gene shuttle vector that expressed human STIM1 Immunoprecipitation studies revealed that STIM1 binds to nucleotide binding fold-1 (NBF1) of the sulfonylurea receptor 1 (SUR1) subunit of the KATP channel...
December 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27989677/salt-controls-feeding-decisions-in-a-blood-sucking-insect
#10
Gina Pontes, Marcos H Pereira, Romina B Barrozo
Salts are necessary for maintaining homeostatic conditions within the body of all living organisms. Like with all essential nutrients, deficient or excessive ingestion of salts can result in adverse health effects. The taste system is a primary sensory modality that helps animals to make adequate feeding decisions in terms of salt consumption. In this work we show that sodium and potassium chloride salts modulate the feeding behavior of Rhodnius prolixus in a concentration-dependent manner. Feeding is only triggered by an optimal concentration of any of these salts (0...
December 15, 2016: Journal of Insect Physiology
https://www.readbyqxmd.com/read/27934605/generation-of-an-abcc8-heterozygous-mutation-human-embryonic-stem-cell-line-using-crispr-cas9
#11
Dongsheng Guo, Haikun Liu, Ge Gao, Aynisahan Ruzi, Kepin Wang, Han Wu, Keyu Lai, Yanli Liu, Fan Yang, Liangxue Lai, Yin-Xiong Li
The gene of ATP-binding cassette subfamily C member 8 (Abcc8) is cytogenetically located at 11p15.1 and encodes the sulfonylurea receptor (SUR1). SUR1 is a subunit of ATP-sensitive potassium channel (KAPT) in the β-cell regulating insulin secretion. Mutations of ABCC8 are responsible for congenital hyperinsulinism (CHI). Here we reported that an Abcc8 heterozygous mutant cell line was generated by CRISPR/Cas9 technique with 1bp insertion resulting in abnormal splicing on human embryonic stem cell line H1. The phenotypic characteristics of this cell line reveal defective KATP channel and diazoxide-responsive that provides ideal model for molecular pathology research and drug screening for CHI...
November 5, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934599/generation-of-an-abcc8-homozygous-mutation-human-embryonic-stem-cell-line-using-crispr-cas9
#12
Dongsheng Guo, Haikun Liu, Ge Gao, Aynisahan Ruzi, Kepin Wang, Han Wu, Keyu Lai, Yanli Liu, Fan Yang, Liangxue Lai, Yin-Xiong Li
The gene of ATP-binding cassette subfamily C member 8 (Abcc8) is cytogenetically located at 11p15.1 and encodes the sulfonylurea receptor (SUR1). SUR1 is a subunit of ATP-sensitive potassium channel (KAPT) in the β-cell regulating insulin secretion. Mutations of ABCC8 are responsible for congenital hyperinsulinism (CHI). Here we generated an Abcc8 homozygous mutant cell line by CRISPR/Cas9 technique with 22bp deletion resulting in abnormal splicing on human embryonic stem cell line H1. The phenotypic characteristics of this cell line reveal defective KATP channel and diazoxide-unresponsive that provides an ideal model for molecular pathology research and drug screening for CHI...
November 9, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27927103/mechanism-of-action-of-relaxant-effect-of-agastache-mexicana-ssp-mexicana-essential-oil-in-guinea-pig-trachea-smooth-muscle
#13
Andrés Navarrete, Natalia Ávila-Rosas, Mateo Majín-León, José Luis Balderas-López, Alejandro Alfaro-Romero, José Carlos Tavares-Carvalho
CONTEXT: Agastache mexicana ssp. mexicana (Kunth) Lint & Epling (Lamiaceae), popularly known as 'toronjil morado', is used in Mexican traditional medicine for the treatment of several diseases such as hypertension, anxiety and respiratory disorders. OBJECTIVE: This study investigates the relaxant action mechanism of A. mexicana ssp. mexicana essential oil (AMEO) in guinea-pig isolated trachea model. MATERIALS AND METHOD: AMEO was analyzed by GC/MS...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27913935/regulation-of-contractile-responses-of-vascular-smooth-muscle-cells-under-conditions-of-hypoxia-reoxygenation
#14
S V Gusakova, Yu G Birulina, L V Smagliy, I V Kovalev, I V Petrova, A V Nosarev, S N Orlov
We analyzed the effects of hypoxia and reoxygenation on changes in contractile activity in rat aortic smooth muscles. Both hypoxia and reoxygenation induced relaxation of smooth muscle cells precontracted with high-potassium Krebs solution (30 mM KCl) or α1-adrenoceptor agonist phenylephrine. Vasodilation resulted from enhancement of potassium permeability of smooth muscle cell membranes caused by activation of voltage-gated potassium channels (triggered by both precontracting agents) or by opening of ATP-sensitive potassium channels (phenylephrine)...
December 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27906419/sch-79797-a-selective-par1-antagonist-protects-against-ischemia-reperfusion-induced-arrhythmias-in-the-rat-hearts
#15
O Y Mohamed, A A Al-Masri, E A El Eter, R Lateef
OBJECTIVE: Thrombin is implicated in the genesis of arrhythmias and activation of thrombin receptors exacerbated ventricular arrhythmias following coronary artery ligation. The present study was designed to investigate the possible protective effect of the protease-activated receptor-1 antagonist, SCH79797 against ischemia and reperfusion arrhythmias in the rat heart. MATERIALS AND METHODS: Healthy male Wistar rats (250-350 g) were anesthetized with urethane. Coronary artery ligation was performed for 5 minutes followed by 10 minutes reperfusion...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27905383/-the-role-of-atp-dependent-potassium-channels-and-nitric-oxide-system-in-the-neuroprotective-effect-of-preconditioning
#16
O G Deryagin, S A Gavrilova, S V Buravkov, V V Andrianov, G G Yafarova, Kh L Gainutdinov, V B Koshelev
AIM: To study a role of ATP-dependent potassium channels (K+ATP) in the neuroprotective effect of ischemic (IP) and pharmacological (PP) preconditioning and evaluate the dynamics of blood nitric oxide (NO) metabolites in cerebral ischemia. MATERIAL AND METHODS: A model of ischemic stroke induced by the electrocoagulation of a middle cerebral artery (MCA) branch was used in male rats (n=86). Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, and diazoxide, a potassium channel activator, were used...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27890915/pharmacological-evidence-a-new-therapeutic-approach-to-the-treatment-of-chronic-heart-failure-through-sur2b-kir6-1-channel-in-endothelial-cells
#17
Shang Wang, Chao-Liang Long, Jun Chen, Wen-Yu Cui, Yan-Fang Zhang, Hao Zhang, Hai Wang
Both iptakalim (Ipt) and natakalim (Nat) activate the SUR2B/Kir6.1 channel, an ATP-sensitive potassium channel (KATP) subtype, with high selectivity. In this study we investigated the therapeutic effects of Ipt and Nat against isoproterenol-induced chronic heart failure (ISO-CHF) in rats, and demonstrated a new therapeutic approach to the treatment of CHF through activation of the SUR2B/Kir6.1 channel in endothelial cells. In ISO-CHF rats, oral administration of Nat (1, 3, 9 mg·kg(-1)·d(-1)) or Ipt (3 mg·kg(-1)·d(-1)) for 60 days significantly improved cardiac dysfunction, reversed cardiac remodeling, significantly attenuated the pathological increases in BNP levels, and improved endothelial dysfunction by adjusting the balance between endothelin and NO systems...
January 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27871896/gastroprotective-and-ulcer-healing-effects-of-hydroethanolic-extract-of-leaves-of-caryocar-coriaceum-mechanisms-involved-in-the-gastroprotective-activity
#18
Luis Jardelino de Lacerda Neto, Andreza Guedes Barbosa Ramos, Valterlucio Santos Sales, Severino Denicio Gonçalves de Souza, Antonia Thassya Lucas Dos Santos, Larissa Rolim de Oliveira, Marta Regina Kerntopf, Thais Rodrigues de Albuquerque, Henrique Douglas Melo Coutinho, Lucindo Jose Quintans-Júnior, Almir Gonçalves Wanderley, Irwin Rose Alencar de Menezes
This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test...
January 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27852936/the-vasorelaxant-mechanisms-of-methanol-on-isolated-rat-aortic-rings-involvement-of-ion-channels-and-signal-transduction-pathways
#19
Y Bai, Q Zhang, Z Yang, Z Meng, Q Zhao
It is reported that methanol is generally used as an industrial solvent, antifreeze, windshield washer fluid, cooking fuel and perfume. Methanol ingestion can lead to severe metabolic disturbances, blindness, or even death. So far, few studies about its negative effects on cardiovascular system have been reported. The purpose of this study was to determine the vasoactive effect of methanol and roles of ion channels and signal transduction pathways on isolated rat aorta. The results suggested that the mechanism of methanol-induced vasorelaxation at low concentrations (<500 mM) was mediated by ATP-sensitive K(+) (KATP) and L-type Ca(2+) channels, but the mechanism at high concentrations (>600 mM) was related to KATP, voltage-dependent K(+), big-conductance Ca(2+)-activated K(+), L-type Ca(2+) channels as well as prostacyclin, protein kinase C, β-adrenoceptors pathways...
November 16, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27847463/metabolic-therapy-for-temporal-lobe-epilepsy-in-a-dish-investigating-mechanisms-of-ketogenic-diet-using-electrophysiological-recordings-in-hippocampal-slices
#20
REVIEW
Masahito Jr Kawamura, David N Ruskin, Susan A Masino
The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices...
2016: Frontiers in Molecular Neuroscience
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