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ATP sensitive potassium channel

Mohammed Safwan Ali Khan, Nishat Ahmed, Misbah, Mohammed Arifuddin, Zainul Amiruddin Zakaria, Mohammad M Al-Sanea, Syeda Umme Kulsoom Khundmiri, Inshah Ahmed, Saleha Ahmed, Pooi Ling Mok
In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs...
March 16, 2018: Food and Chemical Toxicology
Charles E Norton, Steven S Segal
The sensory neurotransmitter calcitonin gene-related peptide (CGRP) is associated with vasodilation of systemic arteries through activation of ATP-sensitive potassium channels (KATP) in smooth muscle cells (SMCs), however its effects on endothelial cell (EC) membrane potential (Vm) are unresolved. In pulmonary arteries (PAs) of C57BL/6J mice, we questioned whether CGRP would hyperpolarize ECs as well as SMCs. Intact PAs were isolated and immunostained for CGRP to confirm sensory innervation; vessel segments (length, 1-2 mm; diameter ∼150 µm) with intact or denuded endothelium were cannulated and pressurized to 16 cm H2O at 37{degree sign}C...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Ren-Hong Du, Hong-Bin Sun, Zhao-Li Hu, Ming Lu, Jian-Hua Ding, Gang Hu
Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6...
March 14, 2018: Cell Death & Disease
Zhongjian Cheng, Xinggui Shen, Xiaohua Jiang, Huimin Shan, Maria Cimini, Pu Fang, Yong Ji, Joon Young Park, Konstantinos Drosatos, Xiaofeng Yang, Christopher G Kevil, Raj Kishore, Hong Wang
Insufficient hydrogen sulfide (H2 S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H2 S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively), and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF)-induced endothelium-dependent relaxation to acetylcholine (ACh), determined by the presence of eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and prostacyclin (PGI2 ) inhibitor indomethacin (INDO), in SMA from db/db mice but not that from db/+ mice...
February 14, 2018: Redox Biology
Masakazu Kotoda, Tadahiko Ishiyama, Kazuha Mitsui, Sohei Hishiyama, Takashi Matsukawa
PURPOSE: Nicorandil has dual properties and acts as a nitric oxide donor and an ATP-sensitive potassium (KATP ) channel opener. Considering its pharmacological profile, nicorandil might exert protective effects on the brain as well as on the heart. The purpose of this study was to directly evaluate the effect of nicorandil on cerebral blood flow (CBF) in mice using a transcranial Doppler method. METHODS: Under general anesthesia, the nicorandil groups received a single-bolus intraperitoneal injection of the respective doses of nicorandil (1, 5, or 10 mg/kg), while the control group received vehicle only...
March 5, 2018: Journal of Anesthesia
Matthew Riopel, Jong Bae Seo, Gautam K Bandyopadhyay, Pingping Li, Joshua Wollam, Heekyung Chung, Seung-Ryoung Jung, Anne Murphy, Maria Wilson, Ron de Jong, Sanjay Patel, Deepika Balakrishna, James Bilakovics, Andrea Fanjul, Artur Plonowski, Duk-Su Koh, Christopher J Larson, Jerrold M Olefsky, Yun Sok Lee
We have previously reported that the fractalkine (FKN)/CX3CR1 system represents a novel regulatory mechanism for insulin secretion and β cell function. Here, we demonstrate that chronic administration of a long-acting form of FKN, FKN-Fc, can exert durable effects to improve glucose tolerance with increased glucose-stimulated insulin secretion and decreased β cell apoptosis in obese rodent models. Unexpectedly, chronic FKN-Fc administration also led to decreased α cell glucagon secretion. In islet cells, FKN inhibited ATP-sensitive potassium channel conductance by an ERK-dependent mechanism, which triggered β cell action potential (AP) firing and decreased α cell AP amplitude...
March 5, 2018: Journal of Clinical Investigation
José M Vidal-Taboada, Marco Pugliese, Maria Salvadó, Josep Gámez, Nicole Mahy, Manuel J Rodríguez
The ATP-sensitive potassium (KATP ) channel directly regulates the microglia-mediated inflammatory response following CNS injury. To determine the putative role of the KATP channel in amyotrophic lateral sclerosis (ALS) pathology, we investigated whether ALS induces changes in KATP channel expression in the spinal cord and motor cortex. We also characterized new functional variants of human ABCC8, ABCC9, KCNJ8, and KCNJ11 genes encoding for the KATP channel and analyzed their association with ALS risk, rate of progression, and survival in a Spanish ALS cohort...
February 28, 2018: Molecular Neurobiology
Isil Ocal, Mehmet B Yilmaz, Sabriye Kocaturk-Sel, Turan Tufan, Mehmet A Erkoc, Gamze Comertpay, Hale Oksuz, Esma D Barc
Diabetes mellitus is a metabolic disease that causes increased morbidity and mortality in developed and developing countries. With recent advancements in technology, alternative treatment methods have begun to be investigated in the world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on vascular complications and contractile activities of aortic rings along with Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (KATP ) in aortas of controlled-diabetic and non-controlled diabetic rats...
February 15, 2018: Bioelectromagnetics
Maurizio Turzo, Julian Vaith, Felix Lasitschka, Markus A Weigand, Cornelius J Busch
BACKGROUND: ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 has been reported in animal models of endotoxemia, we studied the expression and physiological effects of Kir6.1 in murine endotoxemic lungs. We hypothesized that inhibition of overexpressed Kir6...
February 13, 2018: Respiratory Research
Atsumi Saito, Kazuya Miyagawa, Hiroko Miyagishi, Kazuhiro Kurokawa, Akira Umeda, Yasumasa Okada, Minoru Tsuji, Hiroshi Takeda
ATP-sensitive potassium (KATP ) channels consist of two structurally different subunits: a pore-forming subunit of the Kir6.0-family (Kir6.1 or Kir6.2) and a regulatory sulfonylurea receptor subunit (SUR1, SUR2A or SUR2B). Although Kir6.2 is widely distributed in the brain, the mechanisms that underlie the impact of Kir6.2 on emotional behavior are not yet fully understood. To clarify the role of Kir6.2 in emotional behavior, in the present study, we investigated the behavioral characteristics of Kir6.2-knockout (Kir6...
February 10, 2018: Physiology & Behavior
Katherine Lord, Diva D De León
Hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in infants. Prompt recognition and treatment, independent of whether infants have transient or permanent HI, are essential to decrease risk of neurologic damage. The most common form of congenital HI is due to inactivating mutations of the β-cell ATP-sensitive potassium (KATP ) channel (KATP -HI) and is typically diazoxide unresponsive. KATP -HI occurs in diffuse and focal forms. Distinguishing between the 2 forms is crucial, because pancreatectomy is curative in the focal form but palliative in the diffuse form...
March 2018: Clinics in Perinatology
Ramazan Bal, Gurkan Ozturk, Ebru Onalan Etem, Aydin Him, Nurattin Cengiz, Tuncay Kuloglu, Mehmet Tuzcu, Caner Yildirim, Ahmet Tektemur
Major voltage-activated ionic channels of stellate cells in the ventral part of cochlear nucleus (CN) were largely characterized previously. However, it is not known if these cells are equipped with other ion channels apart from the voltage-sensitive ones. In the current study, it was aimed to study subunit composition and function of ATP-sensitive potassium channels (KATP) in stellate cells of the ventral cochlear nucleus. Subunits of KATP channels, Kir6.1, Kir6.2, SUR1, and SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN tissue...
January 29, 2018: Journal of Membrane Biology
Joo Young Kim, Wen Hao Wu, Jin Hyun Jun, Jeenah Sohn, Yong Soo Seo
Objective: Corticotropin-releasing hormone (CRH) is a crucial regulator of human pregnancy and parturition. Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels are important for regulating myometrial quiescence during pregnancy. We investigated regulatory effects of different concentrations of CRH on KATP channel expression in human myometrial smooth muscle cells (HSMCs) in in vitro conditions. Methods: After treating HSMCs with different concentrations of CRH (1, 10, 102, 103, 104 pmol/L), mRNA and protein expression of KATP channel subunits (Kir6...
January 2018: Obstetrics & Gynecology Science
Juan Ramón Martínez-François, María Carmen Fernández-Agüera, Nidhi Nathwani, Carolina Lahmann, Veronica L Burnham, Nika N Danial, Gary Yellen
Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad (<u>B</u>CL-2<u>a</u>gonist of cell<u>d</u>eath) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (KATP ) channels. Here we investigated the effect of BAD manipulation on KATP channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal KATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability...
January 25, 2018: ELife
Jovana Rajkovic, Miodrag Peric, Jelena Stanisic, Jelena Rakocevic, Radmila Novakovic, Vladimir Djokic, Milica Labudovic-Borovic, Snezana Tepavcevic, Vladimir Zivanovic, Vladimir Kanjuh, Helmut Heinle, Ljiljana Gojkovic-Bukarica
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Kaige Peng, Jun Hu, Jingsong Xiao, Guorong Dan, Likui Yang, Feng Ye, Zhongmin Zou, Jia Cao, Yan Sai
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. Mitochondrial dysfunction has been the focus of the pathogenesis of PD. The mitochondrial ATP-sensitive potassium channel (mitoKATP) plays a significant role in mitochondrial physiology and has been extensively shown to protect against ischemic and brain reperfusion injury. However, there have long been controversies regarding its role in Parkinson's disease. We investigated the role of mitoKATP channels in rotenone-induced PD model in vivo and vitro and the interactions of mitoKATP channels, mitochondrial dynamics and PD...
April 2018: Biochimica et Biophysica Acta
A Loppini, M G Pedersen, M Braun, S Filippi
The importance of gap-junction coupling between β cells in pancreatic islets is well established in mouse. Such ultrastructural connections synchronize cellular activity, confine biological heterogeneity, and enhance insulin pulsatility. Dysfunction of coupling has been associated with diabetes and altered β-cell function. However, the role of gap junctions between human β cells is still largely unexplored. By using patch-clamp recordings of β cells from human donors, we previously estimated electrical properties of these channels by mathematical modeling of pairs of human β cells...
September 2017: Physical Review. E
Pedro Marques, Rupert Spencer, Patrick J Morrison, Ian M Carr, Mary N Dang, David T Bonthron, Steven Hunter, Márta Korbonits
CONTEXT: Pseudoacromegaly describes conditions with an acromegaly related physical appearance without abnormalities in the growth hormone (GH) axis. Acromegaloid facies, together with hypertrichosis, are typical manifestations of Cantú syndrome. CASE DESCRIPTION: We present a three-generation family with 5 affected members, with marked acromegaloid facies and prominent hypertrichosis, due to a novel missense variant in the ABCC9 gene. The proband, a 2-year-old girl, was referred due to marked hypertrichosis, noticed soon after birth, associated with coarsening of her facial appearance...
January 11, 2018: Endocrine
Mourad Bouhedja, Basile Peres, Wassim Fhayli, Zeinab Ghandour, Ahcène Boumendjel, Gilles Faury, Smail Khelili
Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC50 < 22 μM) than that of the reference compound diazoxide (EC50 = 24 μM)...
December 21, 2017: European Journal of Medicinal Chemistry
Hongling Hu, Yu Ding, Yang Wang, Shuang Geng, Jue Liu, Jinrong He, Yang Lu, Xueying Li, Mingli Yuan, Shan Zhu, Su Zhao
Previous results have indicated that mitochondrial ATP-sensitive potassium (mitoKATP) channels are associated with the hypoxic proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism underlying the promotive effects of mitoKATP channels on cell proliferation in response to hypoxia remains unknown. mitoKATP channel opening results in a collapse of mitochondrial membrane potential and generation of mitochondrial reactive oxygen species (ROS). As hypoxia-inducible factor-1α (HIF-1α) is a critical oxygen sensor and major transcriptional regulator of the hypoxic adaptive response, the current study assessed whether mitoKATP opening contributes to the chronic proliferation of human PASMCs (hPASMCs) in collaboration with HIF-1α and its downstream targets under hypoxic conditions...
December 2017: Experimental and Therapeutic Medicine
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