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https://www.readbyqxmd.com/read/27913935/regulation-of-contractile-responses-of-vascular-smooth-muscle-cells-under-conditions-of-hypoxia-reoxygenation
#1
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 2, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27911898/bilaterian-giant-ankyrins-have-a-common-evolutionary-origin-and-play-a-conserved-role-in-patterning-the-axon-initial-segment
#2
Timothy Jegla, Michelle M Nguyen, Chengye Feng, Daniel J Goetschius, Esteban Luna, Damian B van Rossum, Bishoy Kamel, Aditya Pisupati, Elliott S Milner, Melissa M Rolls
In vertebrate neurons, the axon initial segment (AIS) is specialized for action potential initiation. It is organized by a giant 480 Kd variant of ankyrin G (AnkG) that serves as an anchor for ion channels and is required for a plasma membrane diffusion barrier that excludes somatodendritic proteins from the axon. An unusually long exon required to encode this 480Kd variant is thought to have been inserted only recently during vertebrate evolution, so the giant ankyrin-based AIS scaffold has been viewed as a vertebrate adaptation for fast, precise signaling...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27906419/sch-79797-a-selective-par1-antagonist-protects-against-ischemia-reperfusion-induced-arrhythmias-in-the-rat-hearts
#3
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/27905566/early-onset-epileptic-encephalopathy-caused-by-a-reduced-sensitivity-of-kv7-2-potassium-channels-to-phosphatidylinositol-4-5-bisphosphate
#4
Maria Virginia Soldovieri, Paolo Ambrosino, Ilaria Mosca, Michela De Maria, Edoardo Moretto, Francesco Miceli, Alessandro Alaimo, Nunzio Iraci, Laura Manocchio, Alessandro Medoro, Maria Passafaro, Maurizio Taglialatela
Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K(+) current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905383/-the-role-of-atp-dependent-potassium-channels-and-nitric-oxide-system-in-the-neuroprotective-effect-of-preconditioning
#5
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/27903793/the-serotonin-5-ht2c-receptor-and-the-non-addictive-nature-of-classic-hallucinogens
#6
REVIEW
Clinton E Canal, Kevin S Murnane
Classic hallucinogens share pharmacology as serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework...
November 15, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27901358/mdck-cells-are-capable-of-water-secretion-and-reabsorption-in-response-to-changes-in-the-ionic-environment
#7
Janne P Capra, Sinikka M Eskelinen
A prerequisite for tissue electrolyte homeostasis is highly regulated ion and water transport through kidney or intestinal epithelia. In the present work, we monitored changes in the cell and luminal volumes of type II Madin-Darby canine kidney (MDCK) cells grown in a 3D environment in response to drugs, or to changes in the composition of the basal extracellular fluid. Using fluorescent markers and high-resolution spinning disc confocal microscopy, we could show that lack of sodium and potassium ions in the basal fluid (tetramethylammonium chloride (TMACl) buffer) induces a rapid increase in the cell and luminal volumes...
September 1, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27901161/optical-control-of-girk-channels-using-visible-light
#8
Julie B Trads, Jessica Burgstaller, Laura Laprell, David B Konrad, Luis de la Osa de la Rosa, C David Weaver, Herwig Baier, Dirk Trauner, David M Barber
G-protein coupled inwardly rectifying potassium (GIRK) channels are an integral part of inhibitory signal transduction pathways, reducing the activity of excitable cells via hyperpolarization. They play crucial roles in processes such as cardiac output, cognition and the coordination of movement. Therefore, the precision control of GIRK channels is of critical importance. Here, we describe the development of the azobenzene containing molecule VLOGO (Visible Light Operated GIRK channel Opener), which activates GIRK channels in the dark and is promptly deactivated when illuminated with green light...
November 30, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27899943/effects-of-allitridum-on-the-transient-outward-potassium-current-in-rats-with-heart-failure
#9
Xiao-Jing Zhao, Kun Lin, Yu Zhang, Bin Xu, Li Liu, Yi-Cheng Fu, Xi Chen, Zhong-Qi Cai, Zhi-Juan Wu, Yun Huang, Yang Li
OBJECTIVE: To study the effect of allitridum on the transient outward potassium current (Ito) of ventricular myocytes in heart failure (HF). METHODS: The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. RESULTS: The Ito current had a significant decrease in the HF group, compared with the control group...
September 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/27899419/progressive-cl-channel-defects-reveal-disrupted-skeletal-muscle-maturation-in-r6-2-huntington-s-mice
#10
Daniel R Miranda, Monica Wong, Shannon H Romer, Cynthia McKee, Gabriela Garza-Vasquez, Alyssa C Medina, Volker Bahn, Andrew D Steele, Robert J Talmadge, Andrew A Voss
Huntington's disease (HD) patients suffer from progressive and debilitating motor dysfunction. Previously, we discovered reduced skeletal muscle chloride channel (ClC-1) currents, inwardly rectifying potassium (Kir) channel currents, and membrane capacitance in R6/2 transgenic HD mice. The ClC-1 loss-of-function correlated with increased aberrant mRNA processing and decreased levels of full-length ClC-1 mRNA (Clcn1 gene). Physiologically, the resulting muscle hyperexcitability may help explain involuntary contractions of HD...
November 29, 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#11
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27896928/liddle-syndrome-clinical-and-genetic-profiles
#12
Yunying Cui, Anli Tong, Jun Jiang, Fen Wang, Chunyan Li
Liddle syndrome is a rare autosomal dominant monogenic form of hypertension. The authors analyzed clinical and genetic features of 12 cases of Liddle syndrome, the largest sample size ever reported. Clinical data were studied retrospectively. The exon 13 of the β and γ subunits of the epithelial sodium channel were amplified and sequenced in the peripheral blood leukocytes of the patients. The onset age of the 12 patients was 15.5±3.3 years. Their blood pressures were poorly controlled, and serum potassium levels in most patients were <3...
November 29, 2016: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/27895596/reciprocal-modulation-of-ik1-ina-extends-excitability-in-cardiac-ventricular-cells
#13
Anthony Varghese
The inwardly rectifying potassium current (IK1) and the fast inward sodium current (INa) are reciprocally modulated in mammalian ventricular myocytes. An increase in the expression of channels responsible for one of these two currents results in a corresponding increase in expression of the other. These currents are critical in the propagation of action potentials (AP) during the normal functioning of the heart. This study identifies a physiological role for IK1-INa reciprocal modulation in ventricular fiber activation thresholds and conduction...
2016: Frontiers in Physiology
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
#14
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...
November 28, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27890830/time-course-of-glial-changes-in-the-hyperhomocysteinemia-model-of-vascular-cognitive-impairment-and-dementia-vcid
#15
Tiffany L Sudduth, Erica M Weekman, Brittani R Price, Jennifer L Gooch, Abigail Woolums, Christopher M Norris, Donna M Wilcock
Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent co-morbidity with AD. Despite its prevalence, little is known about the molecular mechanisms underlying the cognitive dysfunction resulting from cerebrovascular disease. Astrocytic end-feet almost completely surround intraparenchymal blood vessels in the brain and express a variety of channels and markers indicative of their specialized functions in the maintenance of ionic and osmotic homeostasis and gliovascular signaling...
November 25, 2016: Neuroscience
https://www.readbyqxmd.com/read/27886373/clemizole-hydrochloride-blocks-cardiac-potassium-currents-stably-expressed-in-hek-293-cells
#16
Ling-Jun Jie, Wei-Yin Wu, Gang Li, Guo-Sheng Xiao, Shetuan Zhang, Gui-Rong Li, Yan Wang
BACKGROUND AND PURPOSE: Recent studies showed that clemizole has a potential therapeutic effect for hepatitis C infection and also potently inhibits TRPC5 channels. The aim of the present study was to investigate whether clemizole blocks cardiac K(+) currents and affects cardiac repolarization. EXPERIMENTAL APPROACH: Whole-cell patch technique was employed to examine the effects of clemizole on hERG channel current, IKs and Kv1.5 current in HEK 293 cell expression systems as well as on ventricular action potentials of guinea pig hearts...
November 25, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27886263/nicotinic-and-opioid-receptor-regulation-of-striatal-dopamine-d2-receptor-mediated-transmission
#17
Aphroditi A Mamaligas, Yuan Cai, Christopher P Ford
In addition to dopamine neuron firing, cholinergic interneurons (ChIs) regulate dopamine release in the striatum via presynaptic nicotinic receptors (nAChRs) on dopamine axon terminals. Synchronous activity of ChIs is necessary to evoke dopamine release through this pathway. The frequency-dependence of disynaptic nicotinic modulation has led to the hypothesis that nAChRs act as a high-pass filter in the dopaminergic microcircuit. Here, we used optogenetics to selectively stimulate either ChIs or dopamine terminals directly in the striatum...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884747/novel-function-of-%C3%AE-1d-l-type-calcium-channel-in-the-atria
#18
Ujala Srivastava, Ademuyiwa S Aromolaran, Frank Fabris, Deana Lazaro, John Kassotis, Yongxia Qu, Mohamed Boutjdir
Ca entry through atrial L-type Calcium channels (α1C and α1D) play an important role in muscular contraction, regulation of gene expression, and release of hormones including atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP). α1D Ca channel is exclusively expressed in atria, and has been shown to play a key role in the pathogenesis of atrial fibrillation. Recent data have shown that the small conductance calcium-activated potassium channel, SK4 is also atrial specific and also contributes prominently to the secretion of ANP and BNP...
November 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27884343/increased-tolerance-to-stress-in-cardiac-expressed-gain-of-function-of-adenosine-triphosphate-sensitive-potassium-channel-subunit-kir6-1
#19
Matthew C Henn, M Burhan Janjua, Haixia Zhang, Evelyn M Kanter, Carol M Makepeace, Richard B Schuessler, Colin G Nichols, Jennifer S Lawton
BACKGROUND: The adenosine triphosphate-sensitive potassium (KATP) channel opener diazoxide (DZX) prevents myocyte volume derangement and reduced contractility secondary to stress. KATP channels are composed of pore-forming (Kir6.1 or Kir6.2) and regulatory (sulfonylurea receptor, SUR1 or SUR2) subunits. Gain of function (GOF) of Kir6.1 subunits has been implicated in cardiac pathology in Cantu syndrome in humans (cardiomegaly, lymphedema, and pericardial effusions). We hypothesized that GOF of Kir6...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27879055/combining-field-amplified-sample-stacking-with-moving-reaction-boundary-electrophoresis-on-a-paper-chip-for-the-preconcentration-and-separation-of-metal-ions
#20
Liangfei Ouyang, Qian Liu, Heng Liang
A common drawback of paper-based separation devices is their poor detection limit. In this study, we combined field-amplified sample stacking with moving reaction boundary electrophoresis on a paper chip with six array channels for the parallel separation and concentration of multiple samples. With a new hyphenated technique, the brown I2 from the Fe(3+) -I(-) oxidation-reduction reaction emerged near the boundary between the dilute ethylene diamine tetraacetic acid and potassium iodide and highly concentrated KCl solutions...
November 23, 2016: Journal of Separation Science
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