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ATP sensitive potassium channel

Wilfried Dinh, Barbara Albrecht-Küpper, Mihai Gheorghiade, Adriaan A Voors, Michael van der Laan, Hani N Sabbah
Adenosine exerts a variety of physiological effects by binding to cell surface G-protein-coupled receptor subtypes, namely, A1, A2a, A2b, and A3. The central physiological role of adenosine is to preclude tissue injury and promote repair in response to stress. In the heart, adenosine acts as a cytoprotective modulator, linking cardiac function to metabolic demand predominantly via activation of adenosine A1 receptors (A1Rs), which leads to inhibition of adenylate cyclase activity, modulation of protein kinase C, and opening of ATP-sensitive potassium channels...
October 22, 2016: Handbook of Experimental Pharmacology
Shixiao Zhang, Zan Guo, Shijie Yang, Huijuan Ma, Congrui Fu, Sheng Wang, Yi Zhang, Yixian Liu, Jie Hu
OBJECTIVE: Providing adequate protection against cerebral ischemia remains an unrealized goal. The present study was aimed at testing whether chronic intermittent hypobaric hypoxia (CIHH) would have protective effects against cerebral ischemia and investigating the potential role of mitochondrial membrane ATP-sensitive potassium channel (mitoKATP) in this effect. METHODS: Ischemia was induced in rats by occlusion of bilateral common carotid arteries for 8min on day 2 after bilateral vertebral arteries were permanently electrocauterized and CIHH was simulated in a hypoxic chamber...
October 16, 2016: Neuroscience Letters
Amichai Gutgold, David J Gross, Benjamin Glaser, Auryan Szalat
CONTEXT: Hypoglycemia is a rare event in healthy adults, and the differential diagnosis includes many diseases some of which are rare and easily missed. Description of the case: A 20 year-old male military paramedic was referred to our Emergency Department for the investigation of recurrent hypoglycemia episodes during the last months. Factitious hypoglycemia was excluded and organic hyperinsulinemic hypoglycemia was diagnosed by prolonged fast. Imaging studies (endoscopic ultrasound and triple-phase computed tomography) were normal...
October 18, 2016: Journal of Clinical Endocrinology and Metabolism
Kyung Hye Lee, Sang Jin Ha, Jong-Shin Woo, Gi-Ja Lee, So-Ra Lee, Jung Wook Kim, Hun Kuk Park, Weon Kim
BACKGROUND: Exenatide exerts cardioprotective effects by attenuating ischaemic reperfusion injury, possibly through activating the opening of mitochondrial ATP-sensitive potassium channels. We used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties in order to assess exenatide-mediated cardioprotection in IR injury. METHODS: We used an in vivo Sprague-Dawley rat IR model and ex vivo Langendorff injury model. In the left anterior descending artery (LAD) occlusion model, animals were randomly divided into three groups: sham-operated rats (Sham, n=5), IR-injured rats treated with placebo (IR, n=6), and IR-injured treated with exenatide (IR + EXE, n=6)...
September 23, 2016: Heart, Lung & Circulation
Nicola Forte, Lucian Medrihan, Beatrice Cappetti, Pietro Baldelli, Fabio Benfenati
OBJECTIVE: The inhibition of glycolysis exerts potent antiseizure effects, as demonstrated by the efficacy of ketogenic and low-glucose/nonketogenic diets in the treatment of drug-resistant epilepsy. ATP-sensitive potassium (KATP ) channels have been initially identified as the main determinant of the reduction of neuronal hyperexcitability. However, a plethora of other mechanisms have been proposed. Herein, we report the ability of 2-deoxy-d-glucose (2-DG), a glucose analog that inhibits glycolytic enzymes, of potentiating γ-aminobutyric acid (GABA)ergic tonic inhibition via neurosteroid-mediated activation of extrasynaptic GABAA receptors...
October 13, 2016: Epilepsia
Chen Gu
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Many believe autoimmune pathogenesis plays a key role in MS, but its target(s) remains elusive. A recent study detected autoantibodies against KIR4.1, an ATP-sensitive, inward rectifier potassium channel, in nearly half of the MS patients examined. KIR4.1 channels are expressed in astrocytes. Together with aquaporin 4 (AQP4) water channels, they regulate astrocytic functions vital for myelination. Autoantibodies against AQP4 have been established as a key biomarker for neuromyelitis optica (NMO) and contributed to diagnostic and treatment strategy adjustments...
2016: Frontiers in Molecular Neuroscience
Qi Xu, Xiang Wu, Yu Li, Hui Kong, Yu Jin, Weiping Xie, Hong Wang
OBJECTIVES: Pulmonary vascular medial hypertrophy in hypoxic pulmonary arterial hypertension (HPH) is caused in part by decreased apoptosis in pulmonary artery smooth muscle cells (PASMCs). Iptakalim (Ipt), an ATP sensitive potassium channel opener, ameliorates HPH in animal models. Here we investigated the effects of Ipt on proliferation and apoptosis of hypoxic rat PASMCs, and to determine the possible underlying mechanisms. METHODS: Primary rat PASMCs were isolated and cultured...
October 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yan Wu, Meng-Yu He, Jian-Kui Ye, Shu-Ying Ma, Wen Huang, Yong-Yue Wei, Hui Kong, Hong Wang, Xiao-Ning Zeng, Wei-Ping Xie
Accumulating data, including those from our laboratory, have shown that the opening of ATP-sensitive potassium channels (KATP ) plays a protective role in pulmonary vascular diseases (PVD). As maintainers of the endothelial framework, endothelial colony-forming cells (ECFCs) are considered excellent candidates for vascular regeneration in cases of PVD. Although KATP openers (KCOs) have been demonstrated to have beneficial effects on endothelial cells, the impact of KATP on ECFC function remains unclear. Herein, this study investigated whether there is a distribution of KATP in ECFCs and what role KATP play in ECFC modulation...
October 6, 2016: Journal of Cellular and Molecular Medicine
Yukiko Hashimoto, Sumito Dateki, Masakazu Hirose, Kenichi Satomura, Hirotake Sawada, Haruo Mizuno, Shigetaka Sugihara, Koichi Maruyama, Tatsuhiko Urakami, Hidenori Sugawara, Kenji Shirai, Tohru Yorifuji
BACKGROUND: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). OBJECTIVES: To elucidate the characteristics of Japanese patients with KATP-NDM. METHODS: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM...
September 29, 2016: Pediatric Diabetes
Wendy Keung, Lihuan Ren, Sen Li, Andy On-Tik Wong, Anant Chopra, Chi-Wing Kong, Gordon F Tomaselli, Christopher S Chen, Ronald A Li
Human embryonic stem cells (hESCs) is a potential unlimited ex vivo source of ventricular (V) cardiomyocytes (CMs), but hESC-VCMs and their engineered tissues display immature traits. In adult VCMs, sarcolemmal (sarc) and mitochondrial (mito) ATP-sensitive potassium (KATP) channels play crucial roles in excitability and cardioprotection. In this study, we aim to investigate the biological roles and use of sarcKATP and mitoKATP in hESC-VCM. We showed that SarcIK, ATP in single hESC-VCMs was dormant under baseline conditions, but became markedly activated by cyanide (CN) or the known opener P1075 with a current density that was ~8-fold smaller than adult; These effects were reversible upon washout or the addition of GLI or HMR1098...
September 28, 2016: Scientific Reports
Lenka Tomasova, Leszek Dobrowolski, Halina Jurkowska, Maria Wróbel, Tomasz Huc, Karol Ondrias, Ryszard Ostaszewski, Marcin Ufnal
Research suggests that hydrogen sulfide (H2S) is an important biological mediator involved in various physiological processes including the regulation of arterial blood pressure (BP). Although H2S is abundant in the colon, the effects of gut-derived H2S on the circulatory system have not yet been investigated. We studied the effects of intracolonic administration of Na2S, a H2S donor, on systemic hemodynamics. Hemodynamics were recorded in anesthetized, normotensive Wistar Kyoto and spontaneously hypertensive rats at baseline and after intracolonic injection of either saline (controls) or Na2S·9H2O saline solution at a dose range of 10-300 mg/kg of BW...
September 22, 2016: Nitric Oxide: Biology and Chemistry
Haidong Wu, Peng Wang, Yi Li, Manhui Wu, Jiali Lin, Zitong Huang
Objective. We investigated whether and how diazoxide can attenuate brain injury after cardiopulmonary resuscitation (CPR) by selective opening of mitochondrial ATP-sensitive potassium (mitoKATP) channels. Methods. Adult male Sprague-Dawley rats with induced cerebral ischemia (n = 10 per group) received an intraperitoneal injection of 0.1% dimethyl sulfoxide (1 mL; vehicle group), diazoxide (10 mg/kg; DZ group), or diazoxide (10 mg/kg) plus 5-hydroxydecanoate (5 mg/kg; DZ + 5-HD group) 30 min after CPR...
2016: BioMed Research International
Xixun Du, Huamin Xu, Limin Shi, Zhifeng Jiang, Ning Song, Hong Jiang, Junxia Xie
Iron importer divalent metal transporter 1 (DMT1) plays a crucial role in the nigal iron accumulation in Parkinson's disease (PD). Membrane hyperpolarization is one of the factors that could affect its iron transport function. Besides iron, selective activation of the ATP-sensitive potassium (KATP) channels also contributes to the vulnerability of dopaminergic neurons in PD. Interestingly, activation of KATP channels could induce membrane hyperpolarization. Therefore, it is of vital importance to study the effects of activation of KATP channels on DMT1-mediated iron uptake function...
2016: Scientific Reports
Jiseok Baik, Seong-Ho Ok, Eun-Jin Kim, Dawon Kang, Jeong-Min Hong, Il-Woo Shin, Heon Keun Lee, Young-Kyun Chung, Youngil Cho, Soo Hee Lee, Sebin Kang, Ju-Tae Sohn
The goal of this in vitro study was to investigate the effect of mepivacaine on vasodilation induced by the ATP-sensitive potassium (KATP) channel opener levcromakalim in isolated endothelium-denuded rat aortas. The effects of mepivacaine and the KATP channel inhibitor glibenclamide, alone or in combination, on levcromakalim-induced vasodilation were assessed in the isolated aortas. The effects of mepivacaine or combined treatment with a protein kinase C (PKC) inhibitor, GF109203X, and mepivacaine on this vasodilation were also investigated...
July 5, 2016: Canadian Journal of Physiology and Pharmacology
Elizabeth Haythorne, D Lee Hamilton, John A Findlay, Craig Beall, Rory J McCrimmon, Michael L J Ashford
Individuals with Type 1 diabetes (T1D) are often exposed to recurrent episodes of hypoglycaemia. This reduces hormonal and behavioural responses that normally counteract low glucose in order to maintain glucose homeostasis, with altered responsiveness of glucose sensing hypothalamic neurons implicated. Although the molecular mechanisms are unknown, pharmacological studies implicate hypothalamic ATP-sensitive potassium channel (KATP) activity, with KATP openers (KCOs) amplifying, through cell hyperpolarization, the response to hypoglycaemia...
December 2016: Neuropharmacology
Jessica Sabourin, Florent Allagnat
Normal plasma glucose level is ensured by the action of insulin, the major hypoglycemic hormone. Therefore, it is not surprising that insulin release from pancreatic β-cells of the Langerhans islets is controlled by an array of balanced mechanisms in which glucose plays the leading role. Glucose triggers insulin secretion through the well described pathway of ATP-driven closure of ATP-sensitive potassium channels (KATP), depolarization of the plasma membrane and opening of the voltage-dependent Ca2+ channels (VDCC)...
September 2, 2016: Journal of Molecular Endocrinology
Gregory M Martin, Emily A Rex, Prasanna Devaraneni, Jerod S Denton, Kara E Boodhansingh, Diva D DeLeon, Charles A Stanley, Show-Ling Shyng
ATP-sensitive potassium (KATP) channels play a key role in mediating glucose-stimulated insulin secretion by coupling metabolic signals to β-cell membrane potential. Loss of KATP channel function due to mutations in ABCC8 or KCNJ11, genes encoding the sulfonylurea receptor 1 (SUR1) or the inwardly rectifying potassium channel Kir6.2, respectively, results in congenital hyperinsulinism. Many SUR1 mutations prevent trafficking of channel proteins from the endoplasmic reticulum to the cell surface. Channel inhibitors, including sulfonylureas and carbamazepine, have been shown to correct channel trafficking defects...
October 14, 2016: Journal of Biological Chemistry
Antonia Katsouda, Sofia-Iris Bibli, Anastasia Pyriochou, Csaba Szabo, Andreas Papapetropoulos
Recent studies have implicated endogenously produced H2S in the angiogenic process. On one hand, pharmacological inhibition and silencing of the enzymes involved in H2S synthesis attenuate the angiogenic properties of endothelial cells, including proliferation, migration and tube-like structure network formation. On the other hand, enhanced production of H2S by substrate supplementation or over-expression of H2S-producing enzymes leads to enhanced angiogenic responses in cultured endothelial cells. Importantly, H2S up-regulates expression of the key angiogenic factor vascular endothelial growth factor (VEGF) and contributes to the angiogenic signaling in response to VEGF...
August 26, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tomonori Shimbo, Takeshi Adachi, Susumu Fujisawa, Mai Hongoh, Takayoshi Ohba, Kyoichi Ono
The lower esophageal sphincter (LES) is a specialized region of the esophageal smooth muscle that allows the passage of a swallowed bolus into the stomach. Nitric oxide (NO) plays a major role in LES relaxation. Nicorandil possesses dual properties of a NO donor and an ATP-sensitive potassium channel (KATP channel) agonist, and is expected to reduce LES tone. This study investigated the mechanisms underlying the effects of nicorandil on the LES. Rat LES tissues were placed in an organ bath, and activities were recorded using an isometric force transducer...
August 2016: Journal of Pharmacological Sciences
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