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Sodium channel

He Huang, Yao-Jun Zhang, Yong-Zhen Fan, Xi Wu, Christos V Bourantas
RATIONALE: Chronic total occlusion continues to be a challenging lesion subset for percutaneous coronary intervention. PATIENT CONCERNS: A 65-year-old male patient was admitted with symptoms of angina pectoris for 9 months. DIAGNOSES: Coronary angiography showed a severe stenosis in the proximal left anterior descending artery and a chronic total occlusion (CTO) in the proximal right coronary artery. The complexity of the CTO was stratified using the J-CTO score and the PROGRESS CTO score...
July 2018: Medicine (Baltimore)
J David Spence
Resistant hypertension (failure to achieve target blood pressures with three or more antihypertensive drugs including a diuretic) is an important and preventable cause of stroke. Hypertension is highly prevalent in China (>60% of persons above age 65), and only ~6% of hypertensives in China are controlled to target levels. Most strokes occur among persons with resistant hypertension; approximately half of strokes could be prevented by blood pressure control. Reasons for uncontrolled hypertension include (1) non-compliance; (2) consumption of substances that aggravated hypertension, such as excess salt, alcohol, licorice, decongestants and oral contraceptives; (3) therapeutic inertia (failure to intensify therapy when target blood pressures are not achieved); and (4) diagnostic inertia (failure to investigate the cause of resistant hypertension)...
June 2018: Stroke and Vascular Neurology
Maria A Loroño-Pino, Ana Uitz-Mena, Claudia M Carrillo-Solís, Rocío J Zapata-Gil, Dora M Camas-Tec, Lourdes G Talavera-Aguilar, Rosa C Cetina-Trejo, Luis F Flores-Flores, María C Puc-Tinal, Clara Caamal-Jiménez, Guadalupe Reyes-Solís, Julián E García-Rejón, Karla Saavedra-Rodriguez, Lars Eisen, Thomas J Keefe, William C Black Iv, Barry J Beaty
Dengue, chikungunya, yellow fever, and Zika viruses transmitted by Aedes aegypti mosquitoes are major public health threats in the tropical and subtropical world. In México, construction of large tracts of "fraccionamientos" high density housing to accommodate population growth and urbanization has provided fertile ground for Ae. aegypti -transmitted viruses. We investigated the utility of pyrethroid-treated window curtains to reduce both the abundance of Ae. aegypti and to prevent dengue virus (DENV) transmission in fraccionamiento housing...
2018: Journal of Tropical Medicine
Lorena Halty-deLeon, Bill S Hansson, Dieter Wicher
CALX, the Na+ /Ca2+ exchanger in Drosophila , is highly expressed in the outer dendrites of olfactory sensory neurons (OSNs) which are equipped with the odorant receptors (ORs). Insect OR/Orco dimers are nonselective cation channels that pass also calcium which leads to elevated calcium levels after OR activation. CALX exhibits an anomalous regulation in comparison to its homolog in mammals sodium/calcium exchanger, NCX: it is inhibited by increasing intracellular calcium concentration [Ca2+ ]i . Thus, CALX mediates only Ca2+ efflux, not influx...
2018: Frontiers in Cellular Neuroscience
Yali Wang, Elaine Yang, Marta M Wells, Vasyl Bondarenko, Kellie Woll, Vincenzo Carnevale, Daniele Granata, Michael L Klein, Roderic G Eckenhoff, William P Dailey, Manuel Covarrubias, Pei Tang, Yan Xu
Voltage-gated sodium (NaV ) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol...
July 17, 2018: Journal of General Physiology
Kaveh Rayani, Eric Lin, Calvin Craig, Marcel Lamothe, Sanam Shafaattalab, Marvin Gunawan, Alison Yueh Li, Leif Hove-Madsen, Glen F Tibbits
The zebrafish (Danio rerio) heart is a viable model of mammalian cardiovascular function due to similarities in heart rate, ultrastructure, and action potential morphology. Zebrafish are able to tolerate a wide range of naturally occurring temperatures through altering chronotropic and inotropic properties of the heart. Optical mapping of cannulated zebrafish hearts can be used to assess the effect of temperature on excitation-contraction (EC) coupling and to explore the mechanisms underlying voltage (Vm ) and calcium (Ca2+ ) transients...
July 11, 2018: Progress in Biophysics and Molecular Biology
Muhammad M Hossain, Blair Weig, Kenneth Reuhl, Marla Gearing, Long-Jun Wu, Jason R Richardson
Parkinson's disease (PD), the second most common age-related progressive neurodegenerative disorder, is characterized by dopamine depletion and the loss of dopaminergic (DA) neurons with accompanying neuroinflammation. Zonisamide is an-anti-convulsant drug that has recently been shown to improve clinical symptoms of PD through its inhibition of monoamine oxidase B (MAO-B). However, zonisamide has additional targets, including voltage-gated sodium channels (Nav ), which may contribute to its reported neuroprotective role in preclinical models of PD...
July 12, 2018: Experimental Neurology
Sajjad Farashi, Pezhman Sasanpour, Hashem Rafii-Tabar
The effect of temperature variations on the pancreatic β-cell activity and the role of different model compartments in temperature sensing have been investigated using a computational modeling approach. The results of our study show that temperature variations by several degrees can change the dynamical states of the β-cell system. In addition, temperature variations can alter the characteristic features of the membrane voltage, which correlates with insulin secretion. Simulation results show that the ion channels such as the L-type calcium, the hERG potassium, sodium channels and the glycolysis pathway are the possible sites for sensing temperature variation...
July 2018: Journal of Thermal Biology
Sali Al-Ansari, Rozita Jalali, Lilian I Plotkin, Antonius L J J Bronckers, Pamela DenBesten, Yan Zhang, Judith E Raber-Durlacher, Jan de Lange, Frederik R Rozema
During enamel development, formation of hydroxyapatite crystals and regulation of pH in the enamel matrix require massive transport of ions. Both ameloblasts and adjacent dental epithelial cells in the stellate reticulum co-express several transmembrane cotransporters/ion-exchangers for transport of ions across plasma membranes. Gap junctions (GJs) enable intercellular exchanges of ions between neighboring cells. This suggests that the ameloblasts and other cell layers of the enamel organ, form a functional unit...
2018: Frontiers in Physiology
Kirstine Calloe, Gary L Aistrup, José M Di Diego, Robert J Goodrow, Jacqueline A Treat, Jonathan M Cordeiro
Brugada syndrome (BrS) is an inherited disease associated with ST elevation in the right precordial leads, polymorphic ventricular tachycardia (PVT), and sudden cardiac death in adults. Mutations in the cardiac sodium channel account for a large fraction of BrS cases. BrS manifests in the right ventricle (RV), which led us to examine the biophysical and molecular properties of sodium channel in myocytes isolated from the left (LV) and right ventricle. Patch clamp was used to record sodium current (INa ) in single canine RV and LV epicardial (epi) and endocardial (endo) myocytes...
July 2018: Physiological Reports
Y Sheeba Sherlin, T Vijayakumar, J Binoy, S D D Roy, V S Jayakumar
The drug action of ester type local anesthetic (LA) procaine hydrochloride (PRC HCl) is activated by blocking Na+ ion flow when it binds to the ion channel in the ligand gated sodium ion channel protein. Büchi's model, explains binding action of ester type LA drug with receptor in terms of charge transfer, dipole-dipole, hydrogen bonding and van der Waals interactions through lipophilic, ester and hydrophilic moieties. The present work investigates molecular structural and vibrational spectral features of para amino benzoate group, ester part and tertiary amino group respectively belonging to lipophilic, ester and hydrophilic moieties, accountable for the binding of drug to sodium channel...
July 6, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Nikita A Kuldyushev, Konstantin S Mineev, Antonina A Berkut, Steve Peigneur, Alexander S Arseniev, Jan Tytgat, Eugene V Grishin, Alexander A Vassilevski
Sodium channel alpha-toxins from scorpion venom (α-NaTx) inhibit the inactivation of voltage-gated sodium channels. We used solution NMR to investigate the structure of BeM9 toxin from Mesobuthus eupeus scorpion, a prototype α-NaTx classified as an "α-like" toxin due to its wide spectrum of activity on insect and mammalian channels. We identified a new motif that we named "arginine hand", whereby arginine side chain forms several hydrogen bonds with main chain atoms. The arginine hand was found in the "specificity module", a part of the molecule that dictates toxin selectivity; and just single arginine-to-lysine point mutation drastically changed BeM9 selectivity profile...
July 14, 2018: Proteins
Inneke Willekens, Stefaan J Vandecasteele, Kristof Verhoeven, Frank De Geeter
Erythromelalgia is a rare condition characterized by attacks of intensely painful, red and warm feet and/or hands. Symptoms typically are triggered by heat and relieved by cooling of the extremities. Primary cases are due to mutations in the gene for a sodium channel expressed in nociceptive and sympathetic ganglion neurons; secondary causes include blood disorders, infections, drugs, connective tissue diseases, neuropathic diseases, including diabetic neuropathy, and malignancies. We present bone scan findings in a case of erythromelalgia in an 18 years old student, in whom the symptoms developed suddenly...
July 12, 2018: Hellenic Journal of Nuclear Medicine
Nur Siti Khadijah Ramli, Nelli Giribabu, Naguib Salleh
Effects of testosterone on expression and functional activity of ENaC, CFTR and NHE in vas deferens were investigated. METHODS: Orchidectomized, adult male rats were given 125 and 250μg/kg/day testosterone subcutaneously, with or without flutamide and finasteride for seven consecutive days. At the end of the treatment, rats were anesthetized and vas deferens were perfused. Changes in vas deferens fluid secretion rate, pH, HCO3 - , Cl- and Na+ concentrations were recorded in the presence of amiloride and Cftr inh-172...
July 9, 2018: Steroids
G A Abalakov, P V Sutyagin
A previously popular antiarrhythmic drug moricizine (ethmozine) is known for its blocking action on the fast sodium channels in cardiomyocytes. Its effects were examined only in isolated cardiomyocytes or in vivo. Here, the effect of moricizine (10 μM) was examined in vitro on perfused right atrial preparation, where it completely reproduced all the previously observed phenomena and disturbed electrical coupling between the working cardiomyocytes in 35.3±3.4 min, which arrested generation of action potentials...
July 12, 2018: Bulletin of Experimental Biology and Medicine
Sara I Liin, Per-Eric Lund, Johan E Larsson, Johan Brask, Björn Wallner, Fredrik Elinder
Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel...
July 12, 2018: Journal of General Physiology
Sirinun Pisamai, Sittiruk Roytrakul, Narumon Phaonakrop, Janthima Jaresitthikunchai, Gunnaporn Suriyaphol
Oral tumors, including highly invasive and metastatic oral melanoma (OM), non-tonsillar oral squamous cell carcinoma (OSCC) and benign tumors (BN), are common neoplasms in dogs. Although these tumors behave differently, limited data of their protein expression profiles have been exhibited, particularly at the proteome level. The present study aimed to i.) characterize peptide-mass fingerprints (PMFs) and identify potential protein candidates of OM, OSCC, BN and normal control subjects, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS), ii...
2018: PloS One
Alexis S Hill, Yehuda Ben-Shahar
Degenerin/Epithelial Sodium Channels (DEG/ENaCs) are a large family of animal-specific non-voltage gated ion channels, with enriched expression in neuronal and epithelial tissues. While neuronal DEG/ENaCs were originally characterized as sensory receptor channels, recent studies indicate that several DEG/ENaC family members are also expressed throughout the central nervous system. Human genome-wide association studies have linked DEG/ENaC-coding genes with several neurologic and psychiatric disorders, including epilepsy and panic disorder...
July 12, 2018: Channels
Wei-Jie Guan, Jia-Cheng Li, Fang Liu, Jian Zhou, Ya-Ping Liu, Chao Ling, Yong-Hua Gao, Hui-Min Li, Jing-Jing Yuan, Yan Huang, Chun-Lan Chen, Rong-Chang Chen, Xue Zhang, Nan-Shan Zhong
Background: Defective airway host-defense (e.g., altered mucus properties, ciliary defects) contributes to the pathogenesis of bronchiectasis. This study aims to determine whether genetic mutations associated with defective airway host-defense are implicated in the pathogenesis of bronchiectasis. Methods: Based on the systematic screening of 32 frequently reported bronchiectasis-associated genes, we performed next-generation sequencing (NGS) on peripheral blood samples from 192 bronchiectasis patients and 100 healthy subjects...
May 2018: Journal of Thoracic Disease
Adam W Ware, Tanya T Cheung, Sahib Rasulov, Ezra Burstein, Fiona J McDonald
Optimal function of the epithelial sodium channel (ENaC) in the distal nephron is key to the kidney's long-term control of salt homeostasis and blood pressure. Multiple pathways alter ENaC cell surface populations, including correct processing and trafficking in the secretory pathway to the cell surface, and retrieval from the cell surface through ubiquitination by the ubiquitin ligase Nedd4-2, clathrin-mediated endocytosis, and sorting in the endosomal system. Members of the Copper Metabolism Murr1 Domain containing (COMMD) family of 10 proteins are known to interact with ENaC...
2018: Frontiers in Physiology
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