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https://www.readbyqxmd.com/read/27882143/expression-of-connexin-43-ion-channels-and-ca-2-handling-proteins-in-rat-pulmonary-vein-cardiomyocytes
#1
Yaqiong Xiao, Xue Cai, Andrew Atkinson, Sunil Jit Logantha, Mark Boyett, Halina Dobrzynski
Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27872214/effects-of-prolonged-anoxia-on-electrical-activity-of-the-heart-in-crucian-carp-carassius-carassius
#2
Elisa Tikkanen, Jaakko Haverinen, Stuart Egginton, Minna Hassinen, Matti Vornanen
The effects of sustained anoxia on cardiac electrical excitability were examined in the anoxia-tolerant Crucian carp (Carassius carassius). The electrocardiogram (ECG) and expression of excitation-contraction coupling genes were studied in fish acclimatised to normoxia in summer (+18°C) or winter (+2°C), and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained bradycardia from a heart rate of 10.3±0.77 to 4.1±0.29 bpm (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when oxygen was restored...
November 21, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27859264/inwardly-rectifying-k-channels-are-major-contributors-to-flow-induced-vasodilation-in-resistance-arteries
#3
Sang Joon Ahn, Ibra S Fancher, Jing-Tan Bian, Chong Xu Zhang, Sarah Schwab, Robert Gaffin, Shane A Phillips, Irena Levitan
AIMS: Inwardly rectifying K(+) (Kir) channels are known to be sensitive to flow, but their role in flow-induced endothelial responses is not known. The goal of this study is to establish the role of Kir channels in flow-induced vasodilation and to provide first insights into the mechanisms responsible for Kir signaling in this process. METHODS AND RESULTS: First, we establish that primary endothelial cells isolated from murine mesenteric arteries express functional Kir2...
November 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27849039/an-insecticide-resistance-breaking-mosquitocide-targeting-inward-rectifier-potassium-channels-in-vectors-of-zika-virus-and-malaria
#4
Daniel R Swale, Darren W Engers, Sean R Bollinger, Aaron Gross, Edna Alfaro Inocente, Emily Days, Fariba Kanga, Reed M Johnson, Liu Yang, Jeffrey R Bloomquist, Corey R Hopkins, Peter M Piermarini, Jerod S Denton
Insecticide resistance is a growing threat to mosquito control programs around the world, thus creating the need to discover novel target sites and target-specific compounds for insecticide development. Emerging evidence suggests that mosquito inward rectifier potassium (Kir) channels represent viable molecular targets for developing insecticides with new mechanisms of action. Here we describe the discovery and characterization of VU041, a submicromolar-affinity inhibitor of Anopheles (An.) gambiae and Aedes (Ae...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807980/convergence-and-sampling-in-determining-free-energy-landscapes-for-membrane-protein-association
#5
Jan Domanski, George Hedger, Robert B Best, Phillip James Stansfeld, Mark S P Sansom
Potential of mean force (PMF) calculations are used to characterize the free energy landscape of protein-lipid and protein-protein association within membranes. Coarse-grained simulations allow binding free energies to be determined with reasonable statistical error. This accuracy relies on defining a good collective variable describing the binding and unbinding transition, and upon criteria for assessing the convergence of the simulation toward representative equilibrium sampling. As examples, we calculate protein-lipid binding PMFs for ANT/cardiolipin and Kir2...
November 3, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27789106/reversible-dilated-cardiomyopathy-caused-by-a-high-burden-of-ventricular-arrhythmias-in-andersen-tawil-syndrome
#6
Saman Rezazadeh, Jiqing Guo, Henry J Duff, Raechel A Ferrier, Brenda Gerull
Andersen-Tawil syndrome (ATS) is caused by mutations in KCNJ2 (Kir2.1). It remains unclear whether dilated cardiomyopathy (DCM) is a primary feature of ATS. We studied a proband with typical physical features of ATS plus DCM and moderate to severe left ventricular dysfunction (left ventricular ejection fraction = 30.5%). Genetic screening revealed a novel mutation in Kir2.1 (c.665T>C, p.L222S). Functional studies showed that this mutation reduced ionic currents in a dominant-negative manner. Suppression of ventricular arrhythmias with bisoprolol led to normalization of left ventricular size and function...
July 27, 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/27762288/the-effects-of-puerarin-on-rat-ventricular-myocytes-and-the-potential-mechanism
#7
Hao Xu, Manxi Zhao, Shenghui Liang, Quanshu Huang, Yunchuan Xiao, Liang Ye, Qinyi Wang, Longmei He, Lanxiang Ma, Hua Zhang, Li Zhang, Hui Jiang, Xiao Ke, Yuchun Gu
Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27751963/inward-rectifying-k-kir2-leak-conductance-dampens-the-excitability-of-lamina-i-projection-neurons-in-the-neonatal-rat
#8
Neil C Ford, Mark L Baccei
Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27747100/altered-left-ventricular-ion-channel-transcriptome-in-a-high-fat-fed-rat-model-of-obesity-insight-into-obesity-induced-arrhythmogenesis
#9
Reza Ashrafi, Marianne Yon, Lucy Pickavance, Joseph Yanni Gerges, Gershan Davis, John Wilding, Kun Jian, Henggui Zhang, George Hart, Mark Boyett
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR...
2016: Journal of Obesity
https://www.readbyqxmd.com/read/27699887/three-pairs-of-weak-interactions-precisely-regulate-the-g-loop-gate-of-kir2-1-channel
#10
Junwei Li, Shaoying Xiao, Xiaoxiao Xie, Hui Zhou, Chunli Pang, Shanshan Li, Hailin Zhang, Diomedes E Logothetis, Yong Zhan, Hailong An
Kir2.1 (also known as IRK1) plays key roles in regulation of resting membrane potential and cell excitability. To achieve its physiological roles, Kir2.1 performs a series of conformational transition, named as gating. However, the structural basis of gating is still obscure. Here, we combined site-directed mutation, two-electrode voltage clamp with molecular dynamics simulations and determined that H221 regulates the gating process of Kir2.1 by involving a weak interaction network. Our data show that the H221R mutant accelerates the rundown kinetics and decelerates the reactivation kinetics of Kir2...
December 2016: Proteins
https://www.readbyqxmd.com/read/27696527/differential-kv1-3-kca3-1-and-kir2-1-expression-in-classically-and-alternatively-activated-microglia
#11
Hai M Nguyen, Eva M Grössinger, Makoto Horiuchi, Kyle W Davis, Lee-Way Jin, Izumi Maezawa, Heike Wulff
Microglia are highly plastic cells that can assume different phenotypes in response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) promote differentiation into classically activated M1-like microglia, which produce high levels of pro-inflammatory cytokines and nitric oxide and are thought to contribute to neurological damage in ischemic stroke and Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti-inflammatory effects and tissue repair. We here investigated whether these microglia subsets vary in their K(+) channel expression by differentiating neonatal mouse microglia into M(LPS) and M(IL-4) microglia and studying their K(+) channel expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry...
January 2017: Glia
https://www.readbyqxmd.com/read/27598576/mechanisms-underlying-interferon-%C3%AE-induced-priming-of-microglial-reactive-oxygen-species-production
#12
Nicholas G Spencer, Tom Schilling, Francesc Miralles, Claudia Eder
Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME...
2016: PloS One
https://www.readbyqxmd.com/read/27560040/decreased-inward-rectifier-potassium-current-ik1-in-dystrophin-deficient-ventricular-cardiomyocytes
#13
Lena Rubi, Xaver Koenig, Helmut Kubista, Hannes Todt, Karlheinz Hilber
Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current IK1, which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential IK1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models...
August 25, 2016: Channels
https://www.readbyqxmd.com/read/27558197/maguk-scaffolds-organize-a-horizontal-cell-synaptic-complex-restricted-to-invaginating-contacts-with-photoreceptors
#14
Alejandro Vila, Christopher M Whitaker, John O'Brien
Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. As each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes...
August 25, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27540685/styrax-blocks-inward-and-outward-current-of-kir2-1-channel
#15
Shuxi Ren, Chunli Pang, Junwei Li, Yayue Huang, Suhua Zhang, Yong Zhan, Hailong An
Kir2.1 plays key roles in setting rest membrane potential and modulation of cell excitability. Mutations of Kir2.1, such as D172N or E299V, inducing gain-of-function, can cause type3 short QT syndrome (SQT3) due to the enlarged outward currents. So far, there is no clinical drug target to block the currents of Kir2.1. Here, we identified a novel blocker of Kir2.1, styrax, which is a kind of natural compound selected from traditional Chinese medicine. Our data show that styrax can abolish the inward and outward currents of Kir2...
August 12, 2016: Channels
https://www.readbyqxmd.com/read/27527100/structural-basis-of-control-of-inward-rectifier-kir2-channel-gating-by-bulk-anionic-phospholipids
#16
Sun-Joo Lee, Feifei Ren, Eva-Maria Zangerl-Plessl, Sarah Heyman, Anna Stary-Weinzinger, Peng Yuan, Colin G Nichols
Inward rectifier potassium (Kir) channel activity is controlled by plasma membrane lipids. Phosphatidylinositol-4,5-bisphosphate (PIP2) binding to a primary site is required for opening of classic inward rectifier Kir2.1 and Kir2.2 channels, but interaction of bulk anionic phospholipid (PL(-)) with a distinct second site is required for high PIP2 sensitivity. Here we show that introduction of a lipid-partitioning tryptophan at the second site (K62W) generates high PIP2 sensitivity, even in the absence of PL(-) Furthermore, high-resolution x-ray crystal structures of Kir2...
September 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27525318/galectin-3-regulates-atrial-fibrillation-remodeling-and-predicts-catheter-ablation-outcomes
#17
Yoshio Takemoto, Rafael J Ramirez, Miki Yokokawa, Kuljeet Kaur, Daniela Ponce-Balbuena, Mohamad C Sinno, B Cicero Willis, Hamid Ghanbari, Steven R Ennis, Guadalupe Guerrero-Serna, Bettina C Henzi, Rakesh Latchamsetty, Roberto Ramos-Mondragon, Hassan Musa, Raphael P Martins, Sandeep V Pandit, Sami F Noujaim, Thomas Crawford, Krit Jongnarangsin, Frank Pelosi, Frank Bogun, Aman Chugh, Omer Berenfeld, Fred Morady, Hakan Oral, José Jalife
OBJECTIVES: To determine whether Gal-3 mediates sustained atrial fibrillation (AF)-induced atrial structural and electrical remodeling and contributes to AF perpetuation. BACKGROUND: Galectin-3 (Gal-3) mediates extracellular matrix remodeling in heart failure, but its role in AF progression remains unexplored. METHODS: We examined intracardiac blood samples from patients with AF (N=55) to identify potential biomarkers of AF recurrence. In a sheep model of tachypacing-induced AF (N=20), we tested the effects of Gal-3 inhibition during AF progression...
April 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/27521093/dynamics-and-molecular-mechanisms-of-ventricular-fibrillation-in-structurally-normal-hearts
#18
REVIEW
José Jalife
Ventricular fibrillation (VF) is the most severe cardiac rhythm disturbance and one of the most important immediate causes of sudden cardiac death. In the structurally normal heart, a small number of stable reentrant sources, perhaps 1 or 2, underlie the mechanism of VF, and the stabilization of the sources, their frequency, and the complexity of the turbulent waves they generate depend on the expression, spatial distribution, and intermolecular interactions of the 2 most important ion channels that control cardiac excitability: the inward rectifier potassium channel, Kir2...
September 2016: Cardiac Electrophysiology Clinics
https://www.readbyqxmd.com/read/27511995/effect-of-ethanol-and-acetaldehyde-at-clinically-relevant-concentrations-on-atrial-inward-rectifier-potassium-current-ik1-separate-and-combined-effect
#19
Z Horakova, P Matejovic, M Pasek, J Hosek, M Simurdova, J Simurda, M Bebarova
Atrial fibrillation is the most common arrhythmia at alcohol consumption. Its pathogenesis is complex, at least partly related to changes of cardiac inward rectifier potassium currents including IK1. Both ethanol and acetaldehyde have been demonstrated to considerably modify IK1 in rat ventricular myocytes. However, analogical data on the atrial IK1 are lacking. The present study aimed to analyse IK1 changes induced by ethanol and acetyldehyde in atrial myocytes. The experiments were performed by the whole cell patch-clamp technique at 23 ± 1°C on enzymatically isolated rat and guinea-pig atrial myocytes as well as on expressed human Kir2...
June 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/27510622/potassium-channels-in-the-cx43-gap-junction-perinexus-modulate-ephaptic-coupling-an-experimental-and-modeling-study
#20
Rengasayee Veeraraghavan, Joyce Lin, James P Keener, Robert Gourdie, Steven Poelzing
It was recently demonstrated that cardiac sodium channels (Nav1.5) localized at the perinexus, an intercalated disc (ID) nanodomain associated with gap junctions (GJ), may contribute to electrical coupling between cardiac myocytes via an ephaptic mechanism. Impairment of ephaptic coupling by acute interstitial edema (AIE)-induced swelling of the perinexus was associated with arrhythmogenic, anisotropic conduction slowing. Given that Kir2.1 has also recently been reported to localize at intercalated discs, we hypothesized that Kir2...
October 2016: Pflügers Archiv: European Journal of Physiology
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