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https://www.readbyqxmd.com/read/28340295/response-of-catalase-of-the-mouse-primary-hepatocytes-to-sodium-dodecylbenzene-sulfonate-and-the-underlying-molecular-mechanisms
#1
Jing Wang, Jiaxi Wang, Lu Zhang, Rutao Liu, Wansong Zong
This study investigated the adverse effects of sodium dodecylbenzene sulfonates (SDBS) on the mouse primary hepatocytes by conducting cell viability, intracellular oxidative stress level and catalase (CAT) activity assays. It was shown that SDBS altered CAT activities, triggered oxidative stress, and thus exhibited cytotoxicity to the hepatocytes. Both the stimulation of intracellular CAT production and the inhibition of molecular CAT activity contributed to intracellular CAT activity change. Molecular mechanisms underlying CAT activity inhibition and structural changes were explored by isothermal titration calorimetry, multi-spectroscopy and molecular docking studies...
March 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28340057/long-term-outcome-of-pulmonary-vein-isolation-in-patients-with-paroxysmal-atrial-fibrillation-and-brugada-syndrome
#2
Giacomo Mugnai, Burak Hünük, Erwin Ströker, Diego Ruggiero, Hugo Enrique Coutino-Moreno, Ken Takarada, Valentina De Regibus, Rajin Choudhury, Juan Pablo Abugattas de Torres, Darragh Moran, Saverio Iacopino, Pasquale Filannino, Giulio Conte, Juan Sieira, Jan Poelaert, Stefan Beckers, Pedro Brugada, Carlo de Asmundis, Gian-Battista Chierchia
Aims: The therapeutical management of atrial fibrillation (AF) in the setting of Brugada syndrome (BS) might be challenging as many antiarrhythmic drugs (AADs) with sodium channel blocking properties might lead to to the development of ventricular arrhythmias. This study sought to evaluate the clinical outcome in a consecutive series of patients with BS having undergone pulmonary vein (PV) isolation by means of radiofrequency (RF) or cryoballoon (CB) ablation and the efficacy of catheter ablation for preventing inappropriate interventions delivered by implantable cardioverter defibrillators (ICD) on a 3-year follow up...
March 9, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339995/long-term-flecainide-therapy-in-type-3-long-qt-syndrome
#3
Ehud Chorin, Rivki Taub, Aron Medina, Nir Flint, Sami Viskin, Jesaia Benhorin
Aims: Type 3 long QT syndrome (LQT3) is caused by gain-of-function mutations in the cardiac sodium channel gene (SCN5A). Previous reports on the long-term use of sodium channel blockers in LQT3 are sparse. The objective of the current study was to evaluate the long-term safety and efficacy of flecainide therapy in patients with LQT3 who carry the D1790G SCN5A mutation. Methods and results: The study population comprised 30 D1790G carriers who were treated with flecainide and followed for 1-215 months (mean 145 ± 54 months, median 140 months)...
February 28, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28339646/tgf-%C3%AE-receptor-inhibition-prevents-ventricular-fibrosis-in-a-mouse-model-of-progressive-cardiac-conduction-disease
#4
Mickael Derangeon, Jérôme Montnach, Cynthia Ore Cerpa, Benoit Jagu, Justine Patin, Gilles Toumaniantz, Aurore Girardeau, Christopher Lh Huang, William H Colledge, Andrew A Grace, Isabelle Baró, Flavien Charpentier
Loss-of-function mutations in SCN5A, the gene encoding Nav1.5 channel, have been associated with inherited progressive cardiac conduction disease (PCCD). We have proposed that Scn5a heterozygous knock-out (Scn5a+/-) mice, which are characterized by ventricular fibrotic remodeling with ageing, represent a model for PCCD. Our objectives were to identify the molecular pathway involved in fibrosis development and prevent its activation. Methods and results: Our study shows that myocardial interstitial fibrosis occurred in Scn5a+/- mice only after 45 weeks of age...
February 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28338073/veratridine-produces-distinct-calcium-response-profiles-in-mouse-dorsal-root-ganglia-neurons
#5
Zainab A Mohammed, Ciara Doran, David Grundy, Mohammed A Nassar
Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an "agonist" in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337975/a-chemical-chaperone-improves-muscle-function-in-mice-with-a-ryr1-mutation
#6
Chang Seok Lee, Amy D Hanna, Hui Wang, Adan Dagnino-Acosta, Aditya D Joshi, Mark Knoblauch, Yan Xia, Dimitra K Georgiou, Jianjun Xu, Cheng Long, Hisayuki Amano, Corey Reynolds, Keke Dong, John C Martin, William R Lagor, George G Rodney, Ergun Sahin, Caroline Sewry, Susan L Hamilton
Mutations in the RYR1 gene cause severe myopathies. Mice with an I4895T mutation in the type 1 ryanodine receptor/Ca(2+) release channel (RyR1) display muscle weakness and atrophy, but the underlying mechanisms are unclear. Here we show that the I4895T mutation in RyR1 decreases the amplitude of the sarcoplasmic reticulum (SR) Ca(2+) transient, resting cytosolic Ca(2+) levels, muscle triadin content and calsequestrin (CSQ) localization to the junctional SR, and increases endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and mitochondrial ROS production...
March 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337315/sodium-channel-blockers
#7
EDITORIAL
Benjamin Blass
No abstract text is available yet for this article.
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28336914/inhibition-of-serum-and-glucocorticoid-regulated-kinase-1-as-novel-therapy-for-cardiac-arrhythmia-disorders
#8
Vassilios J Bezzerides, Aifeng Zhang, Ling Xiao, Bridget Simonson, Santosh A Khedkar, Shiro Baba, Filomena Ottaviano, Stacey Lynch, Katherine Hessler, Alan C Rigby, David Milan, Saumya Das, Anthony Rosenzweig
Alterations in sodium flux (INa) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel NaV1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1). Activation of SGK1 in the heart causes a marked increase in both the peak and late sodium currents leading to prolongation of the action potential duration and an increased propensity to arrhythmia...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336810/role-of-transient-receptor-potential-vanilloid-1-trpv1-in-the-modulation-of-airway-smooth-muscle-tone-and-calcium-handling
#9
Gene T Yocum, Jun Chen, Christine H Choi, Elizabeth A Townsend, Yi Zhang, Dingbang Xu, Xiao Wen Fu, Michael J Sanderson, Charles W Emala
Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on airway nerve fibers that modulates afferent signals resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+ ATPase 2...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28334922/scn2a-deletion-improves-survival-and-brain-heart-dynamics-in-the-kcna1-null-mouse-model-of-sudden-unexpected-death-in-epilepsy-sudep
#10
Vikas Mishra, Bharat K Karumuri, Nicole M Gautier, Rui Liu, Timothy N Hutson, Stephanie L Vanhoof-Villalba, Ioannis Vlachos, Leonidas Iasemidis, Edward Glasscock
People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology, and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings...
March 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#11
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
February 15, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334404/calcium-homeostasis-modulator-1-like-currents-in-rat-fungiform-taste-cells-expressing-amiloride-sensitive-sodium-currents
#12
Albertino Bigiani
Salt reception by taste cells is still the less understood transduction process occurring in taste buds, the peripheral sensory organs for the detection of food chemicals. Although there is evidence suggesting that the epithelial sodium channel (ENaC) works as sodium receptor, yet it is not clear how salt-detecting cells signal the relevant information to nerve endings. Taste cells responding to sweet, bitter, and umami substances release ATP as neurotransmitter through a nonvesicular mechanism. Three different channel proteins have been proposed as conduit for ATP secretion: pannexin channels, connexin hemichannels, and calcium homeostasis modulator 1 (CALHM1) channels...
March 10, 2017: Chemical Senses
https://www.readbyqxmd.com/read/28334294/an-examination-of-the-role-of-l-glutamate-and-inosine-5-monophosphate-in-hedonic-taste-guided-behavior-by-mice-lacking-the-t1r1-t1r3-receptor
#13
Ginger D Blonde, Alan C Spector
The heterodimeric T1R1 + T1R3 receptor is considered critical for normal signaling of L-glutamate and 5'-ribonucleotides in the oral cavity. However, some taste-guided responsiveness remains in mice lacking one subunit of the receptor, suggesting that other receptors are sufficient to support some behaviors. Here, mice lacking both receptor subunits (KO) and wild-type (WT, both n = 13) mice were tested in a battery of behavioral tests. Mice were trained and tested in gustometers with a concentration series of Maltrin-580, a maltodextrin, in a brief-access test (10-s trials) as a positive control...
March 17, 2017: Chemical Senses
https://www.readbyqxmd.com/read/28332266/11-12-epoxyeicosatrienoic-acid-induces-vasodilator-response-in-the-rat-perfused-mesenteric-vasculature
#14
S M Bihzad, M H M Yousif
Epoxyeicosatrienoic acids (EETs) are endogenous ligands that undergo hydrolysis by soluble epoxide hydrolase (sEH). The responses of 11, 12-EET in comparison with other vasodilator agonists including carbachol and sodium nitroprusside (SNP) were investigated. The effect of 1-cyclohexyl-3-dodecyl urea (CDU), a sEH, was tested on the vasodilator effect induced by 11, 12-EET in the perfused mesenteric beds isolated from normo-glycaemic and type-1 STZ-diabetic rats. In the perfused mesenteric beds of control and diabetic animals, 11, 12-EET produced vasodilation in a dose-dependent manner...
January 2017: Autonomic & Autacoid Pharmacology
https://www.readbyqxmd.com/read/28331474/sodium-channel-%C3%AE-subunits-in-epilepsy-location-location-location
#15
Jennifer A Kearney
No abstract text is available yet for this article.
January 2017: Epilepsy Currents
https://www.readbyqxmd.com/read/28330959/predominantly-myalgic-phenotype-caused-by-the-c-3466g-a-p-a1156t-mutation-in-scn4a-gene
#16
Johanna Palmio, Satu Sandell, Michael G Hanna, Roope Männikkö, Sini Penttilä, Bjarne Udd
OBJECTIVE: To characterize the clinical phenotype in patients with p.A1156T sodium channel mutation. METHODS: Twenty-nine Finnish patients identified with the c.3466G>A p.A1156T mutation in the SCN4A gene were extensively examined. In a subsequent study, 63 patients with similar myalgic phenotype and with negative results in myotonic dystrophy type 2 genetic screening (DM2-neg group) and 93 patients diagnosed with fibromyalgia were screened for the mutation. Functional consequences of the p...
March 22, 2017: Neurology
https://www.readbyqxmd.com/read/28326013/molecular-chaperone-calnexin-regulates-the-function-of-drosophila-sodium-channel-paralytic
#17
Xi Xiao, Changyan Chen, Tian-Ming Yu, Jiayao Ou, Menglong Rui, Yuanfen Zhai, Yijing He, Lei Xue, Margaret S Ho
Neuronal activity mediated by voltage-gated channels provides the basis for higher-order behavioral tasks that orchestrate life. Chaperone-mediated regulation, one of the major means to control protein quality and function, is an essential route for controlling channel activity. Here we present evidence that Drosophila ER chaperone Calnexin colocalizes and interacts with the α subunit of sodium channel Paralytic. Co-immunoprecipitation analysis indicates that Calnexin interacts with Paralytic protein variants that contain glycosylation sites Asn313, 325, 343, 1463, and 1482...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28325641/spectrum-of-nondystrophic-skeletal-muscle-channelopathies-in-children
#18
Fouad Al-Ghamdi, Basil T Darras, Partha S Ghosh
BACKGROUND: The nondystrophic skeletal muscle channelopathies are a group of disorders caused by mutations of various voltage-gated ion channel genes, including nondystrophic myotonia and periodic paralysis. METHODS: We identified patients with a diagnosis of muscle channelopathy from our neuromuscular database in a tertiary care pediatric center from 2005 to 2015. We then performed a retrospective review of their medical records for demographic characteristics, clinical features, investigations, treatment, and follow-up...
February 16, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28324649/sulfonamides-as-selective-nav1-7-inhibitors-optimizing-potency-pharmacokinetics-and-metabolic-properties-to-obtain-atropisomeric-quinolinone-am-0466-that-affords-robust-in-vivo-activity
#19
Russell F Graceffa, Alessandro A Boezio, Jessica Able, Steven Altmann, Loren M Berry, Christiane M Boezio, John R Butler, Margaret Y Chu-Moyer, Melanie Cooke, Erin F DiMauro, Thomas A Dineen, Elma Feric Bojic, Robert S Foti, Robert T Fremeau, Angel Guzman-Perez, Hua Gao, Hakan Gunaydin, Hongbing Huang, Liyue Huang, Christopher Ilch, Michael Jarosh, Thomas Kornecook, Charles R Kreiman, Daniel S La, Joseph Ligutti, Benjamin Charles Milgram, Min-Hwa Jasmine Lin, Isaac E Marx, Hanh Nho Nguyen, Emily A Peterson, Gwen Rescourio, John Roberts, Laurie B Schenkel, Roman Shimanovich, Brian Andrew Sparling, John Stellwagen, Kristin Taborn, Karina R Vaida, Jean Wang, John T S Yeoman, Violeta L Yu, Dawn Zhu, Bryan D Moyer, Matthew M Weiss
Due to its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as NaV1.7 inhibitors that demonstrate high levels of selectivity over other NaV isoforms. Herein, we report the discovery and optimization of a novel series of atropisomeric quinolinone sulfonamide inhibitors of NaV1.7, which demonstrate nanomolar inhibition of NaV1.7 and exhibit high levels of selectivity over other sodium channel isoforms...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28321001/comparative-effects-of-an-angiotensin-ii-receptor-blocker-arb-diuretic-vs-arb-calcium-channel-blocker-combination-on-uncontrolled-nocturnal-hypertension-evaluated-by-information-and-communication-technology-based-nocturnal-home-blood-pressure-monitoring%C3%A3-the
#20
Kazuomi Kario, Naoko Tomitani, Hiroshi Kanegae, Hajime Ishii, Kazuaki Uchiyama, Kayo Yamagiwa, Toshihiko Shiraiwa, Tomohiro Katsuya, Tetsuro Yoshida, Kiyomi Kanda, Shinji Hasegawa, Satoshi Hoshide
BACKGROUND: Nocturnal blood pressure (BP) is an independent risk factor of cardiovascular events. The NOCTURNE study, a multicenter, randomized controlled trial (RCT) using our recently developed information and communication technology (ICT) nocturnal home BP monitoring (HBPM) device, was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension (HT).Methods and Results:Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy (100 mg irbesartan daily) were enrolled...
March 17, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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