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Voltage-gated sodium channel

Daryl C Yang, Jennifer R Deuis, Daniel Dashevsky, James Dobson, Timothy N W Jackson, Andreas Brust, Bing Xie, Ivan Koludarov, Jordan Debono, Iwan Hendrikx, Wayne C Hodgson, Peter Josh, Amanda Nouwens, Gregory J Baillie, Timothy J C Bruxner, Paul F Alewood, Kelvin Kok Peng Lim, Nathaniel Frank, Irina Vetter, Bryan G Fry
Millions of years of evolution have fine-tuned the ability of venom peptides to rapidly incapacitate both prey and potential predators. Toxicofera reptiles are characterized by serous-secreting mandibular or maxillary glands with heightened levels of protein expression. These glands are the core anatomical components of the toxicoferan venom system, which exists in myriad points along an evolutionary continuum. Neofunctionalisation of toxins is facilitated by positive selection at functional hotspots on the ancestral protein and venom proteins have undergone dynamic diversification in helodermatid and varanid lizards as well as advanced snakes...
October 18, 2016: Toxins
Hung X Nguyen, Robert D Kirkton, Nenad Bursac
The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes...
October 18, 2016: Nature Communications
Anne-Marie Malfait, Richard J Miller
Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels, and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis...
October 12, 2016: Current Osteoporosis Reports
Benjamin D Menze, Jacob M Riveron, Sulaiman S Ibrahim, Helen Irving, Christophe Antonio-Nkondjio, Parfait H Awono-Ambene, Charles S Wondji
BACKGROUND: Despite the recent progress in establishing the patterns of insecticide resistance in the major malaria vector Anopheles funestus, Central African populations of this species remain largely uncharacterised. To bridge this important gap and facilitate the implementation of suitable control strategies against this vector, we characterised the resistance patterns of An. funestus population from northern Cameroon. METHODS AND FINDINGS: Collection of indoor-resting female mosquitoes in Gounougou (northern Cameroon) in 2012 and 2015 revealed a predominance of An...
2016: PloS One
Yim Ling Mak, Jing Li, Chih-Ning Liu, Shuk Han Cheng, Paul K S Lam, Jinping Cheng, Leo L Chan
Ciguatoxins (CTXs) are natural biotoxins produced by benthic dinoflagellates of the genus Gambierdiscus, which are bioaccumulated and biotransformed along food chains in coral ecosystems. They are neurotoxins that activate voltage-gated sodium channels and disrupt ion conductance in the excitable tissues. Pacific ciguatoxin-1 (P-CTX-1) is the most prevalent and potent CTX congener present in fishes from the Pacific Ocean. In this study, P-CTX-1 was administrated to larval marine medaka (2h post-hatch) via microinjection...
October 1, 2016: Journal of Hazardous Materials
Ryan B Griggs, Leonid M Yermakov, Keiichiro Susuki
Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials generated at the axon initial segment (AIS) are regenerated at nodes of Ranvier through the process of saltatory conduction. Proper formation and maintenance of the molecular structure at the AIS and nodes are required for sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier and regulate the distribution and localization of specialized functional elements, such as voltage-gated sodium channels and mitochondria...
October 4, 2016: Neuroscience Research
T Z Lu, W Kostelecki, C L F Sun, N Dong, J L Pérez Velázquez, Z-P Feng
The spontaneous rhythmic firing of action potentials in pacemaker neurons depends on the biophysical properties of voltage-gated ion channels and background leak currents. The background leak current includes a large K(+) and a small Na(+) component. We previously reported that a Na(+) -leak current via U-type channels is required to generate spontaneous action potential firing in the identified respiratory pacemaker neuron, RPeD1, in the freshwater pond snail Lymnaea stagnalis. We further investigated the functional significance of the background Na(+) current in rhythmic spiking of RPeD1 neurons...
October 6, 2016: European Journal of Neuroscience
Hatice Gumushan-Aktas, Seyhan Altun
Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic, antimicrobial, antifungal, antiprotozoal and anti-inflammatory effects, and is used in cosmetics. The aim of the present study was to investigate the effect of treatment with extracts of leaves and unripened fruits of H. helix on rat prostate cancer cell lines with markedly different metastatic potentials: Mat-LyLu cells (strongly metastatic) and AT-2 cells (weakly metastatic). The effects of the extracts on cell kinetics and migration were determined...
October 2016: Oncology Letters
Courtney C Cocilova, Sarah L Milton
Harmful algal blooms are increasing in frequency and extent worldwide and occur nearly annually off the west coast of Florida where they affect both humans and wildlife. The dinoflagellate Karenia brevis is a key organism in Florida red tides that produces a suite of potent neurotoxins collectively referred to as the brevetoxins (PbTx). Brevetoxins bind to and open voltage gated sodium channels (VGSC), increasing cell permeability in excitable cells and depolarizing nerve and muscle tissue. Exposed animals may thus show muscular and neurological symptoms including head bobbing, muscle twitching, paralysis, and coma; large HABs can result in significant morbidity and mortality of marine life, including fish, birds, marine mammals, and sea turtles...
September 28, 2016: Aquatic Toxicology
Huan Wang, Hong-Fei Wang, Hao Zhang, Chen Wang, Yu-Fang Chen, Rong Ma, Ji-Zhou Xiang, Xin-Ling Du, Qiang Tang
AIM: Voltage-gated sodium channels composed of a pore-forming α subunit and auxiliary β subunits are responsible for the upstroke of the action potential in cardiac myocytes. The pore-forming subunit of the cardiac sodium channel Nav1.5, which is encoded by SCN5A, is the main ion channel that conducts the voltage-gated cardiac sodium current (INa) in cardiac cells. The current study sought to investigate the inhibitory effects of hesperetin (HSP) on human cardiac Nav1.5 channels stably expressed in human embryonic kidney 293 (HEK 293) cells and on the voltage-gated cardiac sodium current (INa) in human atrial myocytes...
October 3, 2016: Acta Pharmacologica Sinica
Francisco J Urbano, Brennon R Luster, Stasia D'Onofrio, Susan Mahaffey, Edgar Garcia-Rill
Synaptic efferents from the PPN are known to modulate the neuronal activity of several intralaminar thalamic regions (e.g., the centrolateral/parafascicular; Cl/Pf nucleus). The activation of either the PPN or Cl/Pf nuclei in vivo has been described to induce the arousal of the animal and an increment in gamma band activity in the cortical electroencephalogram (EEG). The cellular mechanisms for the generation of gamma band oscillations in Reticular Activating System (RAS) neurons are the same as those found to generate gamma band oscillations in other brains nuclei...
2016: Journal of Visualized Experiments: JoVE
U Lakshmanadoss, A Mertens, M Gallagher, I Kutinsky, B Williamson
Inherited arrhythmia syndromes are a known, albeit rare, cause of sudden cardiac arrest which may present with characteristic electrocardiogram changes in patients with structurally normal heart. There are a variety of distinct arrhythmogenic syndromes that arise from mutations in voltage gated sodium channels, resulting in either gain or loss of function. We describe a patient with a primary inherited arrhythmia syndrome which presented as sudden cardiac arrest. Further workup revealed that her arrest was due to a combination of Brugada syndrome and Long QT3 syndrome secondary to a deleterious mutation of voltage-gated, sodium channel, type V alpha subunit (SCN5A Thr1709Met)...
March 2016: Indian Pacing and Electrophysiology Journal
Hui-Min Yao, Gan Wang, Ya-Ping Liu, Ming-Qiang Rong, Chuan-Bin Shen, Xiu-Wen Yan, Xiao-Dong Luo, Ren Lai
The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp...
September 2016: Chinese Journal of Natural Medicines
Nahit Rizaner, Rustem Onkal, Scott P Fraser, Alessandro Pristerá, Kenji Okuse, Mustafa B A Djamgoz
The possible association of intracellular Ca(2+) with metastasis in human cancer cells is poorly understood. We have studied Ca(2+) signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca(2+) was measured using a membrane-permeant fluorescent Ca(2+)-indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca(2+) oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively)...
October 2016: European Biophysics Journal: EBJ
S Miranda, M Le Besnerais, V Langlois, Y Benhamou, H Lévesque
Erythromelalgia is a rare intermittent vascular acrosyndrome characterized by the combination of recurrent burning pain, warmth and redness of the extremities. It is considered in its primary form as an autosomal dominant neuropathy related to mutations of SCN9A, the encoding gene of a voltage-gated sodium channel subtype Nav1.7. Secondary erythromelalgia is associated with myeloproliferative disorders, drugs (bromocriptine, calcium channel blockers), or clinical conditions such as rheumatic diseases or viral infection...
September 14, 2016: La Revue de Médecine Interne
Vaishali Bane, Sharon Hutchinson, Aisling Sheehan, Brid Brosnan, Paul Barnes, Mary Lehane, Ambrose Furey
Tetrodotoxin (TTX), often referred to as the 'puffer fish' poison, is a marine toxin and it has been identified as the agent responsible for many food poisoning incidents around the world. It is a neurotoxin that blocks voltage-gated sodium channels, resulting in respiratory paralysis and even death in severe cases. It is known to occur in many different species of fish and other organisms. The toxin is mainly found in the Southeast Asia region. Worryingly, TTX is starting to appear in European waters. It is suspected that this is a consequence of Lessepsian migration, also known as the Erythrean invasion...
October 17, 2016: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
Lukas Klumpp, Efe C Sezgin, Franziska Eckert, Stephan M Huber
Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial-mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood-brain barrier, formation of metastatic niches, and colonization in the brain...
2016: International Journal of Molecular Sciences
Rebecca Garcia-Sosa, Linda C Laux
Researchers from the University of Washington in Seattle studied selective heterozygous and homozygous deletions of the voltage gated sodium channel (Nav1.1) in parvalbumin (PV) or somato-statin (SST) expressing interneurons.
May 2016: Pediatric neurology briefs
Nicolaus G Adams, Alison Robertson, Lynn M Grattan, Steve Pendleton, Sparkle Roberts, J Kathleen Tracy, Vera L Trainer
The Makah Tribe of Neah Bay, Washington, has historically relied on the subsistence harvest of coastal seafood, including shellfish, which remains an important cultural and ceremonial resource. Tribal legend describes visitors from other tribes that died from eating shellfish collected on Makah lands. These deaths were believed to be caused by paralytic shellfish poisoning, a human illness caused by ingestion of shellfish contaminated with saxitoxins, which are produced by toxin-producing marine dinoflagellates on which the shellfish feed...
July 2016: Harmful Algae
Linlin Yang, Quanmin Li, Xinming Liu, Shiguang Liu
Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1...
2016: International Journal of Molecular Sciences
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