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https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#1
Claudia Paola Alvarez, Marijana Stagljar, D Ranjith Muhandiram, Voula Kanelis
The sulfonylurea receptor 1 (SUR1) protein forms the regulatory subunit in ATP sensitive K+ (KATP) channels in the pancreas. SUR proteins are members of the ATP-binding cassette (ABC) superfamily of proteins. Binding and hydrolysis of MgATP at the SUR nucleotide binding domains (NBDs) lead to channel opening. Pancreatic KATP channels play an important role in insulin secretion. SUR1 mutations that result in increased channel opening ultimately inhibit insulin secretion and lead to neonatal diabetes. In contrast, SUR1 mutations that disrupt trafficking and/or decrease gating of KATP channels cause congenital hyperinsulinism, where over secretion of insulin occurs even in the presence of low glucose...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28334715/potassium-channel-independent-relaxing-influence-of-adipose-tissue-on-mouse-carotid-artery
#2
Marta Laskowski, Cathrin Andersson, Emilie Eliasson, Veronika Golubinskaya, Holger Nilsson
Since the cardiovascular consequences of obesity reportedly vary in different types of obesity, we investigated the influence of adipose tissue from different locales on the phenylephrine-induced tone of the mouse carotid artery. Vessels were mounted in a Mulvany-Halpern-type wire myograph, and adipose tissue, from the back (brown) or mesenteric or inguinal subcutaneous (white), was placed around the artery. Contractile responses to phenylephrine were not affected by brown adipose tissue but were reduced (p < 0...
March 24, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28333380/smooth-muscle-ion-channels-and-regulation-of-vascular-tone-in-resistance-arteries-and-arterioles
#3
Nathan R Tykocki, Erika M Boerman, William F Jackson
Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body's tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28332176/a-naphthoquinone-from-sinningia-canescens-inhibits-inflammation-and-fever-in-mice
#4
Luís A Lomba, Paulo H Vogt, Victor E P Souza, Mariane C G Leite-Avalca, Maria H Verdan, Maria Elida A Stefanello, Aleksander R Zampronio
We previously showed that plants from the genus Sinningia are a source of antiinflammatory and analgesic compounds with different mechanisms of action. The present study evaluated the antiinflammatory, antinociceptive, and antipyretic effects of a crude extract (CE) from Sinningia canescens, its fractions, and 6-methoxy-7-hydroxy-α-dunnione (MHD) in mice. These effects were evaluated using carrageenan (Cg)-induced paw edema, acetic acid- and formalin-induced nociception, mechanical hyperalgesia, lipopolysaccharide (LPS)-induced fever, and plasma cytokine levels...
March 22, 2017: Inflammation
https://www.readbyqxmd.com/read/28322929/exogenous-h2s-prevents-high-glucose-induced-damage-to-osteoblasts-through-regulation-of-katp-channels
#5
Yuanyuan Liu, Jianyong Liu, Xin Li, Fantao Wang, Xin Xu, Chunling Wang
Association between diabetes and osteoporosis has been extensively investigated. However, whether the effects of H2S on osteoblast function under high glucose (HG) condition relate to ATP-sensitive potassium (KATP) channels is unclear. To investigate the effects of H2S on the proliferation, apoptosis, and mineralization of osteoblasts under HG condition, and to observe whether H2S exert this effect through the KATP channels. Primary osteoblasts (POBs) were obtained from the calvaria of Sprague-Dawley rats. Cells were pre-treated with 400 μmol/L NaHS (a H2S donor), and/or 0...
March 16, 2017: Biochimie
https://www.readbyqxmd.com/read/28294142/inosine-attenuates-spontaneous-activity-in-the-rat-neurogenic-bladder-through-an-a2b-pathway
#6
Claire Doyle, Vivian Cristofaro, Bryan S Sack, Stefan N Lukianov, Mattias Schäfer, Yeun Goo Chung, Maryrose P Sullivan, Rosalyn M Adam
Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28291959/the-opening-of-atp-sensitive-k-channels-protects-h9c2-cardiac-cells-against-the-high-glucose-induced-injury-and-inflammation-by-inhibiting-the-ros-tlr4-necroptosis-pathway
#7
Weijie Liang, Meiji Chen, Dongdan Zheng, Jianhao Li, Mingcai Song, Wenzhu Zhang, Jianqiang Feng, Jun Lan
BACKGROUND/AIMS: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. METHODS: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults...
February 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28270043/roles-of-atp-sensitive-potassium-channel-in-modulating-gastric-tone-and-accommodation-in-dogs
#8
Shiying Li, Yong Lei, Jiande Dz Chen
OBJECTIVE: The ATP sensitive potassium (KATP) channel plays an important role in the regulation of resting membrane potential and membrane excitability. The role of the KATP channel in modulating gastric motility is unclear. The aim of this study was to investigate the role and mechanism of the KATP channel in modulating gastric tone and accommodation in dogs. MATERIALS AND METHODS: Gastric volume under a constant pressure reflecting gastric tone was measured using a barostat device in dogs equipped with a gastric cannula...
May 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28268304/cardiac-katp-channel-modulation-by-16hz-magnetic-fields-a-theoretical-study
#9
Yuval Aharonovich, Mickey Scheinowitz, Sharon Zlochiver
Heart exposure to 16Hz magnetic fields (MFs) was shown to be cardio-protective for diseased hearts; still, the mechanism of this effect is unknown. We hypothesize that a possible one mechanism is an increased trans-membrane KATP channel open probability due to modulation of the degree of dissociation between K+ ions, having a resonance frequency of 16Hz, and the channel selectivity filter. The Fan-Makielski Markovian KATP channel model was adopted, and the MF bio-effect was manifested by modulating the open probability of the channel using the predictive MF bio-effect parameter based on Binhi's quantum mechanics model...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28262846/antiseizure-effects-of-ketogenic-diet-on-seizures-induced-with-pentylenetetrazole-4-aminopyridine-and-strychnine-in-wistar-rats
#10
E O Sanya, A O Soladoye, O O Desalu, P M Kolo, L A Olatunji, J K Olarinoye
The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days...
March 6, 2017: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
https://www.readbyqxmd.com/read/28262438/neonatal-diabetes-and-the-katp-channel-from-mutation-to-therapy
#11
REVIEW
Frances M Ashcroft, Michael C Puljung, Natascia Vedovato
Activating mutations in one of the two subunits of the ATP-sensitive potassium (KATP) channel cause neonatal diabetes (ND). This may be either transient or permanent and, in approximately 20% of patients, is associated with neurodevelopmental delay. In most patients, switching from insulin to oral sulfonylurea therapy improves glycemic control and ameliorates some of the neurological disabilities. Here, we review how KATP channel mutations lead to the varied clinical phenotype, how sulfonylureas exert their therapeutic effects, and why their efficacy varies with individual mutations...
March 2, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28254750/the-roles-of-kca-katp-and-kv-channels-in-regulating-cutaneous-vasodilation-and-sweating-during-exercise-in-the-heat
#12
Jeffrey C Louie, Naoto Fujii, Robert D Meade, Brendan D McNeely, Glen P Kenny
We recently showed the varying roles of Ca(2+)-activated (KCa), ATP-sensitive (KATP) and voltage-gated (KV) K(+) channels in regulating cholinergic cutaneous vasodilation and sweating in normothermic conditions. However, it is unclear whether the respective contributions of these K(+) channels remain intact during dynamic exercise in the heat. Eleven young (23±4 years) males completed a 30-min exercise bout at a fixed rate of metabolic heat production (400 W), followed by a 40-min recovery period in the heat (35°C, 20% relative humidity)...
March 2, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28230659/sulfonylurea-blockade-of-katp-channels-unmasks-a-distinct-type-of-glucose-induced-ca2-decrease-in-pancreatic-%C3%AE-cells
#13
Bo Hellman, Heléne Dansk, Eva Grapengiesser
OBJECTIVES: This study aimed to explore how sulfonylurea blockade of KATP channels affects the early Ca signals for glucose generation of insulin release. METHODS: Cytoplasmic Ca was measured with ratiometric microfluorometry in isolated mouse islets loaded with Fura-PE3. RESULTS: After sulfonylurea blockade of the KATP channels (50 μM-1 mM tolbutamide or 1 μM-1 mM gliclazide), increase of glucose from 3 to 20 mM resulted in suppression of elevated Ca during a 3- to 5-minute period...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28226463/cardiac-katp-channel-modulation-by-16hz-magnetic-fields-a-theoretical-study
#14
Yuval Aharonovich, Mickey Scheinowitz, Sharon Zlochiver, Yuval Aharonovich, Mickey Scheinowitz, Sharon Zlochiver, Yuval Aharonovich, Sharon Zlochiver, Mickey Scheinowitz
Heart exposure to 16Hz magnetic fields (MFs) was shown to be cardio-protective for diseased hearts; still, the mechanism of this effect is unknown. We hypothesize that a possible one mechanism is an increased trans-membrane KATP channel open probability due to modulation of the degree of dissociation between K(+) ions, having a resonance frequency of 16Hz, and the channel selectivity filter. The Fan-Makielski Markovian KATP channel model was adopted, and the MF bio-effect was manifested by modulating the open probability of the channel using the predictive MF bio-effect parameter based on Binhi's quantum mechanics model...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28222502/subclinical-doses-of-atp-sensitive-potassium-channel-modulators-prevent-alterations-in-memory-and-synaptic-plasticity-induced-by-amyloid-%C3%AE
#15
Karla Salgado-Puga, Javier Rodríguez-Colorado, Roberto A Prado-Alcalá, Fernando Peña-Ortega
In addition to coupling cell metabolism and excitability, ATP-sensitive potassium channels (KATP) are involved in neural function and plasticity. Moreover, alterations in KATP activity and expression have been observed in Alzheimer's disease (AD) and during amyloid-β (Aβ)-induced pathology. Thus, we tested whether KATP modulators can influence Aβ-induced deleterious effects on memory, hippocampal network function, and plasticity. We found that treating animals with subclinical doses (those that did not change glycemia) of a KATP blocker (Tolbutamide) or a KATP opener (Diazoxide) differentially restrained Aβ-induced memory deficit, hippocampal network activity inhibition, and long-term synaptic plasticity unbalance (i...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28213290/zd0947-a-sulphonylurea-receptor-modulator-detects-functional-sulphonylurea-receptor-subunits-in-murine-vascular-smooth-muscle-atp-sensitive-k-channels
#16
Tadashi Yamamoto, Kohei Takahara, Keiichiro Uchida, Noriyoshi Teramoto
In order to identify functional sulphonylurea receptor (SUR.x) subunits of native ATP-sensitive K(+) channels (KATP channels) in mouse portal vein, the effects of ZD0947, a SUR.x modulator, were investigated on spontaneous portal vein contractions, macroscopic membrane currents and unitary currents recorded (using patch-clamp techniques) in freshly dispersed mouse portal vein myocytes. Spontaneous contractions in mouse portal vein were reversibly reduced by ZD0947 in a concentration-dependent manner (Ki =293nM)...
April 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28212804/potassium-channels-in-regulation-of-vascular-smooth-muscle-contraction-and-growth
#17
W F Jackson
Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca(2+) channels (VGCC), Ca(2+) influx through VGCC, intracellular Ca(2+), and VSM contraction. Membrane potential also affects release of Ca(2+) from internal stores and the Ca(2+) sensitivity of the contractile machinery such that K(+) channels participate in all aspects of regulation of VSM contraction...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28211608/preclinical-characterisation-of-55p0251-a-novel-compound-that-amplifies-glucose-stimulated-insulin-secretion-and-counteracts-hyperglycaemia-in-rodents
#18
Karin Stadlbauer, Barbara Brunmair, Zsuzsanna Lehner, Immanuel Adorjan, Thomas Scherer, Anton Luger, Leonhardt Bauer, Clemens Fürnsinn
AIMS: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action. MATERIALS AND METHODS: Pharmacokinetic properties of 55P0251 were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets, and comparison to established drugs...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28209764/kcnj11-ablation-is-associated-with-increased-nitro-oxidative-stress-during-ischemia-reperfusion-injury-implications-for-human-ischemic-cardiomyopathy
#19
Bo Zhang, Tatiana Novitskaya, Debra G Wheeler, Zhaobin Xu, Elena Chepurko, Ryan Huttinger, Heng He, Saradhadevi Varadharaj, Jay L Zweier, Yanna Song, Meng Xu, Frank E Harrell, Yan Ru Su, Tarek Absi, Mark J Kohr, Mark T Ziolo, Dan M Roden, Christian M Shaffer, Cristi L Galindo, Quinn S Wells, Richard J Gumina
BACKGROUND: Despite increased secondary cardiovascular events in patients with ischemic cardiomyopathy (ICM), the expression of innate cardiac protective molecules in the hearts of patients with ICM is incompletely characterized. Therefore, we used a nonbiased RNAseq approach to determine whether differences in cardiac protective molecules occur with ICM. METHODS AND RESULTS: RNAseq analysis of human control and ICM left ventricular samples demonstrated a significant decrease in KCNJ11 expression with ICM...
February 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28188160/endogenous-hydrogen-sulfide-contributes-to-uterine-quiescence-during-pregnancy
#20
Xingji You, Zixi Chen, Huina Zhao, Chen Xu, Weina Liu, Qianqian Sun, Ping He, Hang Gu, Xin Ni
Recent evidence suggests that uterine activation for labor is associated with inflammation within uterine tissues. Hydrogen sulfide (H2S) plays a critical role in inflammatory responses in various tissues. Our previous study has shown that human myometrium produces H2S via its generating enzymes cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) during pregnancy. We therefore explored whether H2S plays a role in the maintenance of uterine quiescence during pregnancy. Human myometrial biopsies were obtained from pregnant women at term...
February 10, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
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