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voltage-gated Na channel

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https://www.readbyqxmd.com/read/27924282/a-computationally-efficient-algorithm-for-fitting-ion-channel-parameters
#1
Zachary R Teed, Jonathan R Silva
Continuous time Markov models have been widely used to describe ion channel kinetics, providing explicit representation of channel states and transitions. Fitting models to experimental data remains a computationally demanding task largely due to the high cost of model evaluation. Here, we propose a method to efficiently optimize model parameters and structure. Voltage clamp channel protocols can be decomposed into a series of fixed steps of constant voltage resulting in a set of linear systems of differential equations...
2016: MethodsX
https://www.readbyqxmd.com/read/27918045/modeling-ion-permeation-through-a-bacterial-voltage-gated-calcium-channel-cavab-using-molecular-dynamics-simulations
#2
Jamal Adiban, Yousef Jamali, Hashem Rafii-Tabar
Activation of voltage-gated calcium channels by action potentials leads to the influx of Ca(2+) ions. In this study, the ion permeation characteristics in bacterial voltage-gated calcium (CaVAb) channels were investigated using molecular dynamics simulations. Furthermore, the potential of mean force (PMF) calculations was evaluated to determine the free energy profile for the permeation of cations (Ca(2+) and Na(+)) and anions (Cl(-)) in the CaVAb channel. The results showed that both Ca(2+) and Na(+) cations experienced a deep energy well, while the Cl(-) anion experienced a relatively high energy barrier at the center of the selectivity filter (site 2)...
December 5, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27913935/regulation-of-contractile-responses-of-vascular-smooth-muscle-cells-under-conditions-of-hypoxia-reoxygenation
#3
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/27911746/new-insight-in-cold-pain-role-of-ion-channels-modulation-and-clinical-perspectives
#4
Stéphane Lolignier, Dimitra Gkika, David Andersson, Enrico Leipold, Irina Vetter, Felix Viana, Jacques Noël, Jérôme Busserolles
Cold temperature detection involves the process of sensory transduction in cutaneous primary sensory nerve terminals, which converts thermal stimuli into depolarizations of the membrane. This transformation into electrical signals is followed by the subsequent propagation of action potentials in cold-sensitive afferent nerve fibers. A large array of ion channels shapes this process; however, the precise contribution of specific ion channel subtypes to cold perception and cold pain remains elusive. This review aims at giving an update on our current understanding of the role played by TRPs, leak K(+) and voltage-gated Na(+) and K(+) channels in the transduction of cold by nociceptors and in cold-induced pain...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27907137/voltage-gated-na-channel-isoforms-and-their-mrna-expression-levels-and-protein-abundance-in-three-electric-organs-and-the-skeletal-muscle-of-the-electric-eel-electrophorus-electricus
#5
Biyun Ching, Jia M Woo, Kum C Hiong, Mel V Boo, Wai P Wong, Shit F Chew, Yuen K Ip
This study aimed to obtain the coding cDNA sequences of voltage-gated Na+ channel (scn) α-subunit (scna) and β-subunit (scnb) isoforms from, and to quantify their transcript levels in, the main electric organ (EO), Hunter's EO, Sach's EO and the skeletal muscle (SM) of the electric eel, Electrophorus electricus, which can generate both high and low voltage electric organ discharges (EODs). The full coding sequences of two scna (scn4aa and scn4ab) and three scnb (scn1b, scn2b and scn4b) were identified for the first time (except scn4aa) in E...
2016: PloS One
https://www.readbyqxmd.com/read/27902689/using-intrinsic-flavoprotein-and-nad-p-h-imaging-to-map-functional-circuitry-in-the-main-olfactory-bulb
#6
Cedric R Uytingco, Adam C Puche, Steven D Munger
Neurons exhibit strong coupling of electrochemical and metabolic activity. Increases in intrinsic fluorescence from either oxidized flavoproteins or reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] in the mitochondria have been used as an indicator of neuronal activity for the functional mapping of neural circuits. However, this technique has not been used to investigate the flow of olfactory information within the circuitry of the main olfactory bulb (MOB). We found that intrinsic flavoprotein fluorescence signals induced by electrical stimulation of single glomeruli displayed biphasic responses within both the glomerular (GL) and external plexiform layers (EPL) of the MOB...
2016: PloS One
https://www.readbyqxmd.com/read/27888095/modulation-of-voltage-gated-conductances-of-retinal-horizontal-cells-by-uv-excited-tio2-nanoparticles
#7
Xenia Meshik, Min Choi, Adam Baker, R Paul Malchow, Leigha Covnot, Samuel Doan, Souvik Mukherjee, Sidra Farid, Mitra Dutta, Michael A Stroscio
This study examines the ability of optically-excited titanium dioxide nanoparticles to influence voltage-gated ion channels in retinal horizontal cells. Voltage clamp recordings were obtained in the presence and absence of TiO2 and ultraviolet laser excitation. Significant current changes were observed in response to UV light, particularly in the -40 mV to +40 mV region where voltage-gated Na(+) and K(+) channels have the highest conductance. Cells in proximity to UV-excited TiO2 exhibited a left-shift in the current-voltage relation of around 10 mV in the activation of Na(+) currents...
November 22, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27881775/a-biophysical-model-for-cytotoxic-cell-swelling
#8
Koen Dijkstra, Jeannette Hofmeijer, Stephan A van Gils, Michel J A M van Putten
: We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in conditions of low energy supply, as observed in cerebral ischemia. Our model contains Hodgkin-Huxley-type ion currents, a recently discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts changes in ion gradients and cell swelling during ischemia of various severity or channel blockage with realistic timescales...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27871874/functional-and-immuno-reactive-characterization-of-a-previously-undescribed-peptide-from-the-venom-of-the-scorpion-centruroides-limpidus
#9
Timoteo Olamendi-Portugal, Rita Restano-Cassulini, Lidia Riaño-Umbarila, Baltazar Becerril, Lourival D Possani
A previously undescribed toxic peptide named Cl13 was purified from the venom of the Mexican scorpion Centruroides limpidus. It contains 66 amino acid residues, including four disulfide bonds. The physiological effects assayed in 7 different subtypes of voltage gated Na(+)-channels, showed that it belongs to the β-scorpion toxin type. The most notorious effects were observed in subtypes Nav1.4, Nav1.5 and Nav1.6. Although having important sequence similarities with two other lethal toxins from this scorpion species (Cll1m and Cll2), the recently developed single chain antibody fragments (scFv) of human origin were not capable of protecting against Cl13...
November 18, 2016: Peptides
https://www.readbyqxmd.com/read/27864845/activity-of-the-anticonvulsant-lacosamide-in-experimental-and-human-epilepsy-via-selective-effects-on-slow-na-channel-inactivation
#10
Dominik Holtkamp, Thoralf Opitz, Isabelle Niespodziany, Christian Wolff, Heinz Beck
OBJECTIVE: In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting ~30% of patients with epilepsy. Many classical antiepileptic drugs target voltage-gated sodium channels, and their potent activity in inhibiting high-frequency firing has been attributed to their strong use-dependent blocking action. In chronic epilepsy, a loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels...
November 19, 2016: Epilepsia
https://www.readbyqxmd.com/read/27861438/cardiotoxic-antiemetics-metoclopramide-and-domperidone-block-cardiac-voltage-gated-na-channels
#11
Carsten Stoetzer, Marc Voelker, Thorben Doll, Joerg Heineke, Florian Wegner, Andreas Leffler
BACKGROUND: Metoclopramide and domperidone are prokinetic and antiemetic substances often used in clinical practice. Although domperidone has a more favorable side effect profile and is considered the first-line agent, severe cardiac side effects were reported during the administration of both substances. Cardiac Na channels are common targets of therapeutics inducing cardiotoxicity. Therefore, the aim of this study was to investigate whether the differential cardiotoxicities of metoclopramide and domperidone correlate with the block of Na channels...
November 17, 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27832602/activity-dependent-formation-and-location-of-voltage-gated-sodium-channel-clusters-at-a-cns-nerve-terminal-during-postnatal-development
#12
Jie Xu, Emmanuelle Berret, Jun Hee Kim
In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Nav) channels clustered at nodes of Ranvier. Changes in Nav channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. Here, we studied the activity-dependent formation of Nav channel clusters before and after hearing onset at P12 in the rat and mouse auditory brainstem. In rats, the Nav channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Nav channel cluster at the nodes was present before hearing onset...
November 9, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27827821/early-bioelectric-activities-mediate-redox-modulated-regeneration
#13
Fernando Ferreira, Guillaume Luxardi, Brian Reid, Min Zhao
Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplays between biochemical and biophysical signals during regeneration remain poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidases-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulate the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (JI) during regeneration...
November 8, 2016: Development
https://www.readbyqxmd.com/read/27819327/structure-and-function-of-fs50-a-salivary-protein-from-the-flea-xenopsylla-cheopis-that-blocks-the-sodium-channel-nav1-5
#14
Xueqing Xu, Bei Zhang, Shilong Yang, Su An, José M C Ribeiro, John F Andersen
Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 μM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816572/characterization-of-an-insect-heterodimeric-voltage-gated-sodium-channel-with-unique-alternative-splicing-mode
#15
Xuan-Zhao Jiang, Yu-Xia Pei, Wei Lei, Ke-Yi Wang, Feng Shang, Hong-Bo Jiang, Jin-Jun Wang
Recent discovery of the heterodimeric voltage-gated sodium channels (Nav) in two aphid species, Acyrthosiphon pisum and Myzus persicae, aroused interest in exploring whether this kind of channel is conserved for aphids. Herewith, we aim to provide evidence for the conservation of heterodimeric Navs in aphids and investigate whether they have unique splicing patterns. We found that the only identifiable Nav from Toxoptera citricida consisted of two subunits, forming a heterodimeric Nav, which carried an atypical "DENS" ion selectivity filter and a conventional "MFM" inactivation gate, confirming the heterodimeric Navs' conservation within aphids...
November 3, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27798132/gi-dreadd-expression-in-peripheral-nerves-produces-ligand-dependent-analgesia-as-well-as-ligand-independent-functional-changes-in-sensory-neurons
#16
Jami L Saloman, Nicole N Scheff, Lindsey M Snyder, Sarah E Ross, Brian M Davis, Michael S Gold
: Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers. Whereas baseline heat thresholds in both male and female mice expressing Gi-DREADD were normal, 1 mg/kg clozapine-N-oxide (CNO) produced a significant 3 h increase in heat threshold that returned to baseline by 5 h after injection...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27767232/comparative-electrophysiology-of-retinal-m%C3%A3-ller-glial-cells-a-survey-on-vertebrate-species
#17
Thomas Pannicke, T Ivo Chao, Miriam Reisenhofer, Mike Francke, Andreas Reichenbach
Müller cells are the dominant macroglial cells in the retina of all vertebrates. They fulfill a variety of functions important for retinal physiology, among them spatial buffering of K(+) ions and uptake of glutamate and other neurotransmitters. To this end, Müller cells express inwardly rectifying K(+) channels and electrogenic glutamate transporters. Moreover, a lot of voltage- and ligand-gated ion channels, aquaporin water channels, and electrogenic transporters are expressed in Müller cells, some of them in a species-specific manner...
October 21, 2016: Glia
https://www.readbyqxmd.com/read/27755281/acidic-ph-modulation-of-na-channels-in-trigeminal-mesencephalic-nucleus-neurons
#18
In-Sik Kang, Jin-Hwa Cho, In-Sun Choi, Do-Yeon Kim, Il-Sung Jang
Cell bodies of trigeminal mesencephalic nucleus (Vmes) neurons are located within the central nervous system, and therefore, peripheral as well as central acidosis can modulate the excitability of Vmes neurons. Here, we report the effect of acidic pH on voltage-gated Na channels in acutely isolated rat Vmes neurons using a conventional whole-cell patch clamp technique. Acidic pH (pH 6.0) slightly but significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials...
October 14, 2016: Neuroreport
https://www.readbyqxmd.com/read/27753830/sy-03-3-overview-of-somatic-mutations-and-epigenetic-regulation-of-aldosterone-producing-adenoma-apa
#19
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27748841/effects-of-adenosine-stimulation-on-the-mrna-expression-of-clcnkb-in-the-basolateral-medullary-thick-ascending-limb-of-the-rat-kidney
#20
Haiyan Luan, Peng Wu, Mingxiao Wang, Hongyu Sui, Lili Fan, Ruimin Gu
Adenosine is a molecule produced by several organs within the body, including the kidneys, where it acts as an autoregulatory factor. It mediates ion transport in several nephron segments, including the proximal tubule and the thick ascending limb (TAL). Ion transport is dictated in part by anionic chloride channels, which regulate crucial kidney functions, including the reabsorption of Na+ and Cl‑, urine concentration, and establishing and maintaining the corticomedullary osmotic gradient. The present study investigated the effects of adenosine on the mRNA expression of chloride voltage‑gated channel Kb (CLCNKB), a candidate gene involved in hypertension, which encodes for the ClC‑Kb channel...
September 26, 2016: Molecular Medicine Reports
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