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https://www.readbyqxmd.com/read/27932952/evaluating-tools-for-live-imaging-of-structural-plasticity-at-the-axon-initial-segment
#1
Adna S Dumitrescu, Mark D Evans, Matthew S Grubb
The axon initial segment (AIS) is a specialized neuronal compartment involved in the maintenance of axo-dendritic polarity and in the generation of action potentials. It is also a site of significant structural plasticity-manipulations of neuronal activity in vitro and in vivo can produce changes in AIS position and/or size that are associated with alterations in intrinsic excitability. However, to date all activity-dependent AIS changes have been observed in experiments carried out on fixed samples, offering only a snapshot, population-wide view of this form of plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27932503/computational-modelling-of-epithelial-fluid-and-ion-transport-in-the-parotid-duct-after-transfection-of-human-aquaporin-1
#2
Shelley Fong, John A Chiorini, James Sneyd, Vinod Suresh
Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemisty of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27932425/scn2b-deletion-in-mice-results-in-ventricular-and-atrial-arrhythmias
#3
Yangyang Bao, B Cicero Willis, Chad R Frasier, Luis F Lopez-Santiago, Xianming Lin, Roberto Ramos-Mondragón, David S Auerbach, Chunling Chen, Zhenxun Wang, Justus Anumonwo, Héctor H Valdivia, Mario Delmar, José Jalife, Lori L Isom
BACKGROUND: Mutations in SCN2B, encoding voltage-gated sodium channel β2-subunits, are associated with human cardiac arrhythmias, including atrial fibrillation and Brugada syndrome. Because of this, we propose that β2-subunits play critical roles in the establishment or maintenance of normal cardiac electric activity in vivo. METHODS AND RESULTS: To understand the pathophysiological roles of β2 in the heart, we investigated the cardiac phenotype of Scn2b null mice...
December 2016: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/27930384/the-endothelial-mineralocorticoid-receptor-mediator-of-the-switch-from-vascular-health-to-disease
#4
Ana P Davel, Imran J Anwar, Iris Z Jaffe
PURPOSE OF REVIEW: Endothelial dysfunction is an early feature of vascular disease induced by cardiovascular risk factors (CRFs). In growing populations with obesity, diabetes, hypertension, and heart failure, mineralocorticoid receptor antagonism improves endothelial function. This review summarizes recent advances in our understanding of the specific role of endothelial cell mineralocorticoid receptor in vascular function in health and disease. RECENT FINDINGS: Using transgenic mice with mineralocorticoid receptor expression specifically modulated in endothelial cells, recent studies support the emerging concept that while endothelial cell mineralocorticoid receptor may be protective in health, in the presence of CRFs, endothelial cell mineralocorticoid receptor activity contributes to endothelial dysfunction and progression of vascular disease...
December 7, 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27929391/a-hyperspectral-survey-of-new-york-city-lighting-technology
#5
Gregory Dobler, Masoud Ghandehari, Steven E Koonin, Mohit S Sharma
Using side-facing observations of the New York City (NYC) skyline, we identify lighting technologies via spectral signatures measured with Visible and Near Infrared (VNIR) hyperspectral imaging. The instrument is a scanning, single slit spectrograph with 872 spectral channels from 0.4-1.0 μ m. With a single scan, we are able to clearly match the detected spectral signatures of 13 templates of known lighting types. However, many of the observed lighting spectra do not match those that have been measured in the laboratory...
December 5, 2016: Sensors
https://www.readbyqxmd.com/read/27924669/effects-of-15%C3%A2-hz-square-wave-magnetic-fields-on-the-voltage-gated-sodium-and-potassium-channels-in-prefrontal-cortex-pyramidal-neurons
#6
Yu Zheng, Jun-Rong Dou, Yang Gao, Lei Dong, Gang Li
PURPOSE: Although magnetic fields have significant effects on neurons, little is known about the mechanisms behind their effects. The present study aimed to measure the effects of magnetic fields on ion channels in cortical pyramidal neurons. MATERIALS AND METHODS: Cortical pyramidal neurons of Kunming mice were isolated and then subjected to 15 Hz, 1 mT square wave (duty ratio 50%) magnetic fields stimulation. Sodium currents (INa), transient potassium currents (IA) and delayed rectifier potassium currents (IK) were recorded by whole-cell patch clamp method...
December 7, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27922499/the-dystrophic-and-nondystrophic-myotonias
#7
Valeria A Sansone
PURPOSE OF REVIEW: This article describes clinical and electrical myotonia and provides an update on the classification, diagnosis, and management of myotonic disorders. RECENT FINDINGS: In the myotonic dystrophies, antisense oligonucleotides provide a general strategy to correct RNA gain of function and modulate the expression of CTG expanded repeats; they are currently being tested in a phase 1-2 randomized controlled trial in patients with adult-onset myotonic dystrophy type 1...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27920129/chronic-inhibition-of-renal-outer-medullary-potassium-channel-not-only-prevented-but-also-reversed-development-of-hypertension-and-end-organ-damage-in-dahl-salt-sensitive-rats
#8
Xiaoyan Zhou, Michael J Forrest, Wanda Sharif-Rodriguez, Gail Forrest, Daphne Szeto, Olga Urosevic-Price, Yonghua Zhu, Andra S Stevenson, Yuchen Zhou, Sloan Stribling, Maya Dajee, Shawn P Walsh, Alexander Pasternak, Kathleen A Sullivan
The renal outer medullary potassium (ROMK) channel mediates potassium recycling and facilitates sodium reabsorption through the Na(+)/K(+)/2Cl(-) cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Evidence from the phenotype of humans and rodents with functional ROMK deficiency supports the contention that selective ROMK inhibitors (ROMKi) will represent a novel diuretic with potential of therapeutic benefit for hypertension. ROMKi have recently been synthesized by Merck & Co, Inc...
December 5, 2016: Hypertension
https://www.readbyqxmd.com/read/27919210/three-dimensional-modelling-of-the-voltage-gated-sodium-ion-channel-from-anopheles-gambiae-reveals-spatial-clustering-of-evolutionarily-conserved-acidic-residues-at-the-extracellular-sites
#9
Rithvik S Vinekar, Ramanathan Sowdhamini
The eukaryotic voltage-gated sodium channel(e-Nav) is a large asymmetric transmembrane protein with important functions concerning neurological function. No structure has been resolved at high resolution for this protein. A homology model of the transmembrane and extracellular regions of an Anopheles gambiae para-like channel with emphasis on the pore entrance has been constructed, based upon the templates provided by a prokaryotic sodium channel and a potassium two-pore channel. The latter provides a template for the extracellular regions, which are located above the entrance to the pore, which is likely to open at a side of a dome formed by these loops...
December 5, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27917859/scn4b-acts-as-a-metastasis-suppressor-gene-preventing-hyperactivation-of-cell-migration-in-breast-cancer
#10
Emeline Bon, Virginie Driffort, Frédéric Gradek, Carlos Martinez-Caceres, Monique Anchelin, Pablo Pelegrin, Maria-Luisa Cayuela, Séverine Marionneau-Lambot, Thibauld Oullier, Roseline Guibon, Gaëlle Fromont, Jorge L Gutierrez-Pajares, Isabelle Domingo, Eric Piver, Alain Moreau, Julien Burlaud-Gaillard, Philippe G Frank, Stéphan Chevalier, Pierre Besson, Sébastien Roger
The development of metastases largely relies on the capacity of cancer cells to invade extracellular matrices (ECM) using two invasion modes termed 'mesenchymal' and 'amoeboid', with possible transitions between these modes. Here we show that the SCN4B gene, encoding for the β4 protein, initially characterized as an auxiliary subunit of voltage-gated sodium channels (NaV) in excitable tissues, is expressed in normal epithelial cells and that reduced β4 protein levels in breast cancer biopsies correlate with high-grade primary and metastatic tumours...
December 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27916464/subtype-specific-block-of-voltage-gated-k-channels-by-%C3%AE-conopeptides
#11
Enrico Leipold, Florian Ullrich, Markus Thiele, Alesia A Tietze, Heinrich Terlau, Diana Imhof, Stefan H Heinemann
The neurotoxic cone snail peptide μ-GIIIA specifically blocks skeletal muscle voltage-gated sodium (NaV1.4) channels. The related conopeptides μ-PIIIA and μ-SIIIA, however, exhibit a wider activity spectrum by also inhibiting the neuronal NaV channels NaV1.2 and NaV1.7. Here we demonstrate that those μ-conopeptides with a broader target range also antagonize select subtypes of voltage-gated potassium channels of the KV1 family: μ-PIIIA and μ-SIIIA inhibited KV1.1 and KV1.6 channels in the nanomolar range, while being inactive on subtypes KV1...
December 1, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27915266/systematic-ajmaline-challenge-in-patients-with-long-qt-3-syndrome-caused-by-the-most-common-mutation-a-multicentre-study
#12
Stephan Hohmann, Boris Rudic, Torsten Konrad, David Duncker, Thorben König, Erol Tülümen, Thomas Rostock, Martin Borggrefe, Christian Veltmann
AIMS: Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K. METHODS AND RESULTS: Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study...
December 2, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27914535/indoxacarb-biotransformation-in-the-german-cockroach
#13
Ameya D Gondhalekar, Ernesto S Nakayasu, Isabel Silva, Bruce Cooper, Michael E Scharf
Insecticides that are used for pest control undergo physical and biological (enzymatic) degradation. Indoxacarb is an oxadiazine class sodium channel blocker insecticide used for German cockroach (Blattella germanica L.) control. At present, no information is available on enzymatic biotransformation or metabolism of indoxacarb in this important urban pest. We studied the biotransformation pathways of indoxacarb in one susceptible and three field strains with varying susceptibility levels using liquid chromatography and high-resolution mass spectrometry...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27913935/regulation-of-contractile-responses-of-vascular-smooth-muscle-cells-under-conditions-of-hypoxia-reoxygenation
#14
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/27906756/optic-neuritis-the-eye-as-a-window-to-the-brain
#15
Thomas M Jenkins, Ahmed T Toosy
PURPOSE OF REVIEW: Acute optic neuritis is a common clinical problem, requiring a structured assessment to guide management and prevent visual loss. The optic nerve is the most accessible part of the central nervous system, so optic neuritis also represents an important paradigm to help decipher mechanisms of damage and recovery in the central nervous system. Important developments include the advent of optical coherence tomography as a biomarker of central nervous system axonal loss, the discovery of new pathological antibodies, notably against aquaporin-4 and, more recently, myelin oligodendrocyte protein, and emerging evidence for sodium channel blockade as a novel therapeutic approach to address energy failure in neuroinflammatory disease...
November 30, 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27906699/reversal-effects-of-local-anesthetics-on-p-glycoprotein-mediated-cancer-multidrug-resistance
#16
Yong Hu, Xiaobing Qin, Haixia Cao, Shaorong Yu, Jifeng Feng
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits...
November 30, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27905525/inhibition-of-cystathionine-%C3%AE-synthetase-suppresses-sodium-channel-activities-of-dorsal-root-ganglion-neurons-of-rats-with-lumbar-disc-herniation
#17
Jun Yan, Shufen Hu, Kang Zou, Min Xu, Qianliang Wang, Xiuhua Miao, Shan Ping Yu, Guang-Yin Xu
The pathogenesis of pain in lumbar disc herniation (LDH) remains poorly understood. We have recently demonstrated that voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons were sensitized in a rat model of LDH. However, the detailed molecular mechanism for sensitization of VGSCs remains largely unknown. This study was designed to examine roles of the endogenous hydrogen sulfide synthesizing enzyme cystathionine β-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905510/remarkable-alterations-of-nav1-6-in-reactive-astrogliosis-during-epileptogenesis
#18
Hongyan Zhu, Yuxiao Zhao, Hao Wu, Nan Jiang, Ziyi Wang, Weide Lin, Jiahui Jin, Yonghua Ji
Voltage-gated sodium channels (VGSCs) play a vital role in controlling neuronal excitability. Nav1.6 is the most abundantly expressed VGSCs subtype in the adult central nervous system and has been found to contribute to facilitate the hyperexcitability of neurons after electrical induction of status epilepticus (SE). To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct animal models of temporal lobe epilepsy (TLE) including a post-SE model induced by kainic acid (KA) intrahippocampal injection and a kindling model evoked by pentylenetetrazole (PTZ)...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905012/microbial-proteins-as-novel-industrial-biotechnology-hosts-to-treat-epilepsy
#19
REVIEW
Zareen Amtul, Amal A Aziz
Epilepsy is characterized by the hyperexcitability of various neuronal circuits that results due to the imbalance between glutamate-mediated excitation of voltage-gated cation channels and γ-amino butyric acid (GABA)-mediated inhibition of anion channels leading to aberrant, sporadic oscillations or fluctuations in neuronal electrical activity. Epilepsy with a risk of mortality and around 65 million sufferers of all ages all over the world is limited therapeutically with high rates of adverse reactions, lack of complete seizure control, and over 30% patients with refractory epilepsy...
December 1, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#20
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
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