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https://www.readbyqxmd.com/read/28635651/effects-of-tetrodotoxin-in-mouse-models-of-visceral-pain
#1
Rafael González-Cano, Miguel Ángel Tejada, Antonia Artacho-Cordón, Francisco Rafael Nieto, José Manuel Entrena, John N Wood, Cruz Miguel Cendán
Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28634443/the-narrow-abdomen-ion-channel-complex-is-highly-stable-and-persists-from-development-into-adult-stages-to-promote-behavioral-rhythmicity
#2
Devon L Moose, Stephanie J Haase, Benjamin T Aldrich, Bridget C Lear
The sodium leak channel NARROW ABDOMEN (NA)/ NALCN is an important component of circadian pacemaker neuronal output. In Drosophila, rhythmic expression of the NA channel regulator Nlf-1 in a subset of adult pacemaker neurons has been proposed to contribute to circadian regulation of channel localization or activity. Here we have restricted expression of Drosophila NA channel subunits or the Nlf-1 regulator to either development or adulthood using the temperature-inducible tubulin-GAL80(ts) system. Surprisingly, we find that developmental expression of endogenous channel subunits and Nlf-1 is sufficient to promote robust rhythmic behavior in adults...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28634442/mild-traumatic-brain-injury-evokes-pyramidal-neuron-axon-initial-segment-plasticity-and-diffuse-presynaptic-inhibitory-terminal-loss
#3
Michal Vascak, Jianli Sun, Matthew Baer, Kimberle M Jacobs, John T Povlishock
The axon initial segment (AIS) is the site of action potential (AP) initiation, thus a crucial regulator of neuronal activity. In excitatory pyramidal neurons, the high density of voltage-gated sodium channels (NaV1.6) at the distal AIS regulates AP initiation. A surrogate AIS marker, ankyrin-G (ankG) is a structural protein regulating neuronal functional via clustering voltage-gated ion channels. In neuronal circuits, changes in presynaptic input can alter postsynaptic output via AIS structural-functional plasticity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28633068/multi-electrode-system-for-measurement-of-transmembrane-ion-fluxes-through-living-epithelial-cells
#4
Mirosław Zając, Andrzej Lewenstam, Krzysztof Dolowy
Cystic Fibrosis (CF) is the most common fatal human genetic disease. It is caused by the defect in a single anion channel protein which affects ion and water transport across the epithelial tissue. A flat multi-electrode platform of diameter 12mm, allowing for measurement of four ions: sodium, potassium, hydrogen and chloride by exchangeable/replaceable ion-selective electrodes is described. The measurement is possible owing to the architecture of the platform which accommodates all the electrodes and inlets/outlets...
June 13, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28630432/down-regulation-of-kca2-3-channels-causes-erectile-dysfunction-in-mice
#5
Simon Comerma-Steffensen, Attila Kun, Elise R Hedegaard, Susie Mogensen, Christian Aalkjaer, Ralf Köhler, Birgitte Mønster Christensen, Ulf Simonsen
Modulation of endothelial calcium-activated K(+) channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K(+) channels (KCa2.3 or SK3) contributes to erectile function. The research was performed in transgenic mice with overexpression (KCa2.3 (T/T(-Dox))) or down-regulation (KCa2.3 (T/T(+Dox))) of the KCa2.3 channels and wild-type C57BL/6-mice (WT). QPCR revealed that KCa2.3 and KCa1.1 channels were the most abundant in mouse corpus cavernosum...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630169/patient-specific-drug-screening-using-a-human-induced-pluripotent-stem-cell-model-of-catecholaminergic-polymorphic-ventricular-tachycardia-type-2
#6
Leonid Maizels, Irit Huber, Gil Arbel, Anke J Tijsen, Amira Gepstein, Asaad Khoury, Lior Gepstein
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) results from autosomal recessive CASQ2 mutations, causing abnormal Ca(2+)-handling and malignant ventricular arrhythmias. We aimed to establish a patient-specific human induced pluripotent stem cell (hiPSC) model of CPVT2 and to use the generated hiPSC-derived cardiomyocytes to gain insights into patient-specific disease mechanism and pharmacotherapy. METHODS AND RESULTS: hiPSC cardiomyocytes were derived from a CPVT2 patient (D307H-CASQ2 mutation) and from healthy controls...
June 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28629594/the-discovery-of-benzoxazine-sulfonamide-inhibitors-of-nav1-7-tools-that-bridge-efficacy-and-target-engagement
#7
Daniel S La, Emily A Peterson, Christiane Bode, Alessandro A Boezio, Howard Bregman, Margaret Y Chu-Moyer, James Coats, Erin F DiMauro, Thomas A Dineen, Bingfan Du, Hua Gao, Russell Graceffa, Hakan Gunaydin, Angel Guzman-Perez, Robert Fremeau, Xin Huang, Christopher Ilch, Thomas J Kornecook, Charles Kreiman, Joseph Ligutti, Min-Hwa Jasmine Lin, Jeff S McDermott, Isaac Marx, David J Matson, Stefan I McDonough, Bryan D Moyer, Hanh Nho Nguyen, Kristin Taborn, Violeta Yu, Matthew M Weiss
The voltage-gated sodium channel NaV1.7 has received much attention from the scientific community due to compelling human genetic data linking gain- and loss-of-function mutations to pain phenotypes. Despite this genetic validation of NaV1.7 as a target for pain, high quality pharmacological tools facilitate further understanding of target biology, establishment of target coverage requirements and subsequent progression into the clinic. Within the sulfonamide class of inhibitors, reduced potency on rat NaV1...
June 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28621020/conservation-of-alternative-splicing-in-sodium-channels-reveals-evolutionary-focus-on-release-from-inactivation-and-structural-insights-into-gating
#8
A Liavas, G Lignani, S Schorge
Voltage-gated sodium channels are critical for neuronal activity, and highly intolerant to variation. Even mutations that cause subtle changes in the activity these channels are sufficient to cause devastating inherited neurological diseases, such as epilepsy and pain. However, these channels do vary in healthy tissue. Alternative splicing modifies sodium channels, but the functional relevance and adaptive significance of this splicing remain poorly understood. Here we use a conserved alternate exon encoding part of the first domain of sodium channels to compare how splicing modifies different channels, and to ask whether the functional consequences of this splicing have been preserved in different genes...
June 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28620319/vascular-endothelial-growth-factor-b-induces-a-distinct-electrophysiological-phenotype-in-mouse-heart
#9
Nikolay Naumenko, Jenni Huusko, Tomi Tuomainen, Jussi T Koivumäki, Mari Merentie, Erika Gurzeler, Kari Alitalo, Riikka Kivelä, Seppo Ylä-Herttuala, Pasi Tavi
Vascular endothelial growth factor B (VEGF-B) is a potent mediator of vascular, metabolic, growth, and stress responses in the heart, but the effects on cardiac muscle and cardiomyocyte function are not known. The purpose of this study was to assess the effects of VEGF-B on the energy metabolism, contractile, and electrophysiological properties of mouse cardiac muscle and cardiac muscle cells. In vivo and ex vivo analysis of cardiac-specific VEGF-B TG mice indicated that the contractile function of the TG hearts was normal...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28620187/discovery-and-identification-of-o-o-diethyl-o-4-5-phenyl-4-5-dihydroisoxazol-3-yl-phenyl-phosphorothioate-xp-1408-as-a-novel-mode-of-action-of-organophosphorus-insecticides
#10
Zhigang Zeng, Ying Yan, Bingfeng Wang, Niu Liu, Hanhong Xu
Organophosphorus (OP) insecticides play an important role in pest control. Many OP insecticides have been removed from the market because of their high toxicity to humans. We designed and synthesized a new OP insecticide with the goal of providing a low cost, and less toxic insecticide. The mode of action of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) was studied in Drosophila melanogaster. Bioassays showed that XP-1408 at a concentration of 50 mg/L delayed larval development...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617689/paracellular-transport-and-energy-utilization-in-the-renal-tubule
#11
Alan S L Yu
PURPOSE OF REVIEW: Paracellular transport across the tight junction is a general mechanism for transepithelial transport of solutes in epithelia, including the renal tubule. However, why paracellular transport evolved, given the existence of a highly versatile system for transcellular transport, is unknown. RECENT FINDINGS: Recent studies have identified the paracellular channel, claudin-2, that is responsible for paracellular reabsorption of sodium in the proximal renal tubule...
June 14, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28615892/molecular-genetics-of-epilepsy-a-clinician-s-perspective
#12
REVIEW
Vikas Dhiman
Epilepsy is a common neurological problem, and there is a genetic basis in almost 50% of people with epilepsy. The diagnosis of genetic epilepsies makes the patient assured of the reasons of his/her seizures and avoids unnecessary, expensive, and invasive investigations. Last decade has shown tremendous growth in gene sequencing technologies, which have made genetic tests available at the bedside. Whole exome sequencing is now being routinely used in the clinical setting for making a genetic diagnosis. Genetic testing not only makes the diagnosis but also has an effect on the management of the patients, for example, the role of sodium channels blockers in SCN1A+ Dravet syndrome patients and usefulness of ketogenic diet therapy in SLC2A1+ generalized epilepsy patients...
April 2017: Annals of Indian Academy of Neurology
https://www.readbyqxmd.com/read/28614116/parathyroid-hormone-and-the-regulation-of-renal-tubular-calcium-transport
#13
Benjamin Ko
PURPOSE OF REVIEW: Renal tubule excretion of calcium is carefully and complexly regulated. At the center of this process, parathyroid hormone (PTH) is the chief regulator of renal calcium reabsorption. This review outlines our current understanding of PTH's effects on renal tubular calcium transport, focusing on the more recent discoveries beyond its direct regulation of epithelial Ca channel transient receptor potential vanilloid 5 (TRPV5) and looking at its interaction with sodium transport and the hormones fibroblast growth factor 23 (FGF23) and klotho...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28613341/three-dimensional-interpenetrating-mesoporous-carbon-confining-sno2-particles-for-superior-sodiation-desodiation-properties
#14
Jagabandhu Patra, Purna Chandra Rath, Cheng-Hsein Yang, Diganta Saikia, Hsien-Ming Kao, Jeng-Kuei Chang
Nanosized SnO2 particles (∼2 nm in diameter) are embedded in ordered mesoporous CMK-8 carbon with unique three-dimensional interconnected pore channels and used as a sodium-ion battery (NIB) anode. Due to the CMK-8 confinement effects, the growth of SnO2 is suppressed during synthesis, leading to high material electroactivity. The CMK-8 not only serves as an electronic conducting pathway, but also creates interpenetrating tunnels, which guarantee electrolyte accessibility and thus Na(+) transport throughout the electrode...
June 14, 2017: Nanoscale
https://www.readbyqxmd.com/read/28613240/an-isoform-of-nedd4-2-plays-a-pivotal-role-in-electrophysiological-cardiac-abnormalities
#15
Shintaro Minegishi, Tomoaki Ishigami, Hisho Kawamura, Tabito Kino, Lin Chen, Rie Nakashima-Sasaki, Hiroshi Doi, Kengo Azushima, Hiromichi Wakui, Yumi Chiba, Kouichi Tamura
We have previously shown that neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) isoforms with a C2 domain are closely related to ubiquitination of epithelial sodium channel (ENaC), resulting in salt-sensitive hypertension by Nedd4-2 C2 targeting in mice. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene encodes the α subunit of the human cardiac voltage-gated sodium channel (I Na), and the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene encodes rapidly activating delayed rectifier K channels (I Kr)...
June 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28612144/fast-calcium-transients-translate-the-distribution-and-conduction-of-neural-activity-in-different-regions-of-a-single-sensory-neuron
#16
Nuhan Purali
In the present study, cytosolic calcium concentration changes were recorded in response to various forms of excitations, using the fluorescent calcium indicator dye OG-BAPTA1 together with the current or voltage clamp methods in stretch receptor neurons of crayfish. A single action potential evoked a rise in the resting calcium level in the axon and axonal hillock, whereas an impulse train or a large saturating current injection would be required to evoke an equivalent response in the dendrite region. Under voltage clamp conditions, amplitude differences between axon and dendrite responses vanished completely...
September 2017: Invertebrate Neuroscience: IN
https://www.readbyqxmd.com/read/28611771/tnf-lectin-like-domain-restores-epithelial-sodium-channel-function-in-frameshift-mutants-associated-with-pseudohypoaldosteronism-type-1b
#17
Anita Willam, Mohammed Aufy, Susan Tzotzos, Dina El-Malazi, Franziska Poser, Alina Wagner, Birgit Unterköfler, Didja Gurmani, David Martan, Shahid Muhammad Iqbal, Bernhard Fischer, Hendrik Fischer, Helmut Pietschmann, Istvan Czikora, Rudolf Lucas, Rosa Lemmens-Gruber, Waheed Shabbir
Previous in vitro studies have indicated that tumor necrosis factor (TNF) activates amiloride-sensitive epithelial sodium channel (ENaC) current through its lectin-like (TIP) domain, since cyclic peptides mimicking the TIP domain (e.g., solnatide), showed ENaC-activating properties. In the current study, the effects of TNF and solnatide on individual ENaC subunits or ENaC carrying mutated glycosylation sites in the α-ENaC subunit were compared, revealing a similar mode of action for TNF and solnatide and corroborating the previous assumption that the lectin-like domain of TNF is the relevant molecular structure for ENaC activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611679/icariin-a-novel-blocker-of-sodium-and-calcium-channels-eliminates-early-and-delayed-afterdepolarizations-as-well-as-triggered-activity-in-rabbit-cardiomyocytes
#18
Wanzhen Jiang, Mengliu Zeng, Zhenzhen Cao, Zhipei Liu, Jie Hao, Peipei Zhang, Youjia Tian, Peihua Zhang, Jihua Ma
Icariin, a flavonoid monomer from Herba Epimedii, has confirmed pharmacological and biological effects. However, its effects on arrhythmias and cardiac electrophysiology remain unclear. Here we investigate the effects of icariin on ion currents and action potentials (APs) in the rabbit myocardium. Furthermore, the effects of icariin on aconitine-induced arrhythmias were assessed in whole rabbits. Ion currents and APs were recorded in voltage-clamp and current-clamp mode in rabbit left ventricular myocytes (LVMs) and left atrial myocytes (LAMs), respectively...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28611355/improved-efficacy-of-an-arthropod-toxin-expressing-fungus-against-insecticide-resistant-malaria-vector-mosquitoes
#19
Etienne Bilgo, Brian Lovett, Weiguo Fang, Niraj Bende, Glenn F King, Abdoulaye Diabate, Raymond J St Leger
The continued success of malaria control efforts requires the development, study and implementation of new technologies that circumvent insecticide resistance. We previously demonstrated that fungal pathogens can provide an effective delivery system for mosquitocidal or malariacidal biomolecules. Here we compared genes from arthropod predators encoding insect specific sodium, potassium and calcium channel blockers for their ability to improve the efficacy of Metarhizium against wild-caught, insecticide-resistant anophelines...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28608751/molecular-modelling-studies-of-kdr-mutations-in-voltage-gated-sodium-channel-revealed-significant-conformational-variations-contributing-to-insecticide-resistance
#20
Nanda Kumar Yellapu, Jeyakodi Gopal, Gunasekaran Kasinahtan, Jambulingam Purushothaman
Voltage gated sodium channels (VGSC) of mosquito vectors are the primary targets of DDT and other synthetic pyrethroids used in public health programs. The knockdown resistant (kdr) mutations in VGSC are associated with the insecticide resistance especially in Anophelines. The present study is aimed to emphasize and demarcate the impact of three kdr-mutations such as L1014S, L1014F and L1014H on insecticide resistance. The membrane model of sodium transport domain of VGSC (STD-VGSC) was constructed using de novo approach based on domain and trans-membrane predictions...
June 13, 2017: Journal of Biomolecular Structure & Dynamics
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