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voltage-gated Na channel

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https://www.readbyqxmd.com/read/28293175/two-photon-na-imaging-reports-somatically-evoked-action-potentials-in-rat-olfactory-bulb-mitral-and-granule-cell-neurites
#1
Tiffany Ona-Jodar, Niklas J Gerkau, S Sara Aghvami, Christine R Rose, Veronica Egger
Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca(2+) imaging. Here, we used two-photon Na(+) imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28265756/sodium-channel-biophysics-late-sodium-current-and-genetic-arrhythmic-syndromes
#2
REVIEW
Karan R Chadda, Kamalan Jeevaratnam, Ming Lei, Christopher L-H Huang
Arrhythmias arise from breakdown of orderly action potential (AP) activation, propagation and recovery driven by interactive opening and closing of successive voltage-gated ion channels, in which one or more Na(+) current components play critical parts. Early peak, Na(+) currents (I Na) reflecting channel activation drive the AP upstroke central to cellular activation and its propagation. Sustained late Na(+) currents (I Na-L) include contributions from a component with a delayed inactivation timecourse influencing AP duration (APD) and refractoriness, potentially causing pro-arrhythmic phenotypes...
March 6, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28257815/gadolinium-released-by-the-linear-gadolinium-based-contrast-agent-gd-dtpa-decreases-the-activity-of-human-epithelial-na-channels-enacs
#3
Fenja Knoepp, Joerg Bettmer, Martin Fronius
BACKGROUND: Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd(3+) ions. Gd(3+) is also a modulator of mechano-gated ion channels, including the epithelial Na(+) channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd(3+) from GBCAs causing the above-mentioned adverse reactions...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28202574/action-potentials-and-ion-conductances-in-wild-type-and-calhm1-knockout-type-ii-taste-cells
#4
Zhongming Ma, Wint Thu Saung, J Kevin Foskett
Taste bud type II cells fire action potentials in response to tastants, triggering non-vesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. Here, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1-knockout (KO) mice...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28195313/neuronal-sodium-channels-emerging-components-of-the-nano-machinery-of-cardiac-calcium-cycling
#5
Rengasayee Veeraraghavan, Sándor Györke, Przemysław B Radwański
Excitation-contraction coupling (ECC) is the bridge between cardiac electrical activation and mechanical contraction. It is driven by the influx of Ca(2+) across the sarcolemma triggering Ca(2+) release from the sarcoplasmic reticulum (SR) - a process termed Ca(2+) -induced Ca(2+) release (CICR) - followed by re-sequestration of Ca(2+) into the SR. The sodium calcium exchanger (NCX) inextricably couples the cycling of Ca(2+) and Na(+) in cardiac myocytes. Thus, influx of Na(+) via voltage-gated Na(+) channels (NaV ) has emerged as an important regulator of CICR both in health and in disease...
February 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28195065/effect-of-econazole-and-benzydamine-on-sensory-neurons-in-culture
#6
S Mathivanan, R de la Torre-Martinez, C Wolf, G Mangano, L Polenzani, C Milanese, A Ferrer-Montiel
Econazole is an anti-mycotic agent widely used for the treatment of cutaneous fungal infections, and for the therapy of vaginal candidiasis. Topical application of this azole is generally safe, although some patients have complained of mild burning sensation/cutaneous irritation and itching, especially when administered intravaginally. The underlying mechanisms responsible of these adverse effects are poorly understood, though they suggest excitation of cutaneous nociceptor terminals. We report that exposure of primary cultures of rat nociceptors to econazole augments neuronal excitability...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28193882/neuronal-hyperexcitability-in-a-mouse-model-of-scn8a-epileptic-encephalopathy
#7
Luis F Lopez-Santiago, Yukun Yuan, Jacy L Wagnon, Jacob M Hull, Chad R Frasier, Heather A O'Malley, Miriam H Meisler, Lori L Isom
Patients with early infantile epileptic encephalopathy (EIEE) experience severe seizures and cognitive impairment and are at increased risk for sudden unexpected death in epilepsy (SUDEP). EIEE13 [Online Mendelian Inheritance in Man (OMIM) # 614558] is caused by de novo missense mutations in the voltage-gated sodium channel gene SCN8A Here, we investigated the neuronal phenotype of a mouse model expressing the gain-of-function SCN8A patient mutation, p.Asn1768Asp (Nav1.6-N1768D). Our results revealed regional and neuronal subtype specificity in the effects of the N1768D mutation...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28191886/sirtuin-1-regulates-cardiac-electrical-activity-by-deacetylating-the-cardiac-sodium-channel
#8
Ajit Vikram, Christopher M Lewarchik, Jin-Young Yoon, Asma Naqvi, Santosh Kumar, Gina M Morgan, Julia S Jacobs, Qiuxia Li, Young-Rae Kim, Modar Kassan, Jing Liu, Mohanad Gabani, Ajay Kumar, Haider Mehdi, Xiaodong Zhu, Xiaoqun Guan, William Kutschke, Xiaoming Zhang, Ryan L Boudreau, Shengchuan Dai, Daniel S Matasic, Saet-Byel Jung, Kenneth B Margulies, Vikas Kumar, Markus M Bachschmid, Barry London, Kaikobad Irani
The voltage-gated cardiac Na(+) channel (Nav1.5), encoded by the SCN5A gene, conducts the inward depolarizing cardiac Na(+) current (INa) and is vital for normal cardiac electrical activity. Inherited loss-of-function mutations in SCN5A lead to defects in the generation and conduction of the cardiac electrical impulse and are associated with various arrhythmia phenotypes. Here we show that sirtuin 1 deacetylase (Sirt1) deacetylates Nav1.5 at lysine 1479 (K1479) and stimulates INa via lysine-deacetylation-mediated trafficking of Nav1...
March 2017: Nature Medicine
https://www.readbyqxmd.com/read/28188741/molecular-dynamics-study-of-ion-transport-through-an-open-model-of-voltage-gated-sodium-channel
#9
Yang Li, Ruining Sun, Huihui Liu, Haipeng Gong
Voltage-gated sodium (NaV) channels are critical in the signal transduction of excitable cells. In this work, we modeled the open conformation for the pore domain of a prokaryotic NaV channel (NaVRh), and used molecular dynamics simulations to track the translocation of dozens of Na(+) ions through the channel in the presence of a physiological transmembrane ion concentration gradient and a transmembrane electrical field that was closer to the physiological one than previous studies. Channel conductance was then estimated from simulations on the wide-type and DEKA mutant of NaVRh...
February 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28182562/in-silico-modeling-of-the-functional-role-of-reduced-sialylation-in-sodium-and-potassium-channel-gating-of-mouse-ventricular-myocytes
#10
Dongping Du, Hui Yang, Andrew R Ednie, Eric S Bennett
Cardiac ion channels are highly glycosylated membrane proteins, with up to 30% of the protein's mass containing glycans. Heart diseases often accompany individuals with congenital disorders of glycosylation (CDG). However, cardiac dysfunction among CDG patients is not yet fully understood. There is an urgent need to study how aberrant glycosylation impacts cardiac electrical signaling. Our previous works reported that congenitally reduced sialylation achieved through deletion of the sialyltransferase gene, ST3Gal4, leads to altered gating of voltage-gated Na+ and K+ channels (Nav and Kv, respectively)...
February 6, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28171721/simulating-the-activation-of-voltage-sensing-domain-for-a-voltage-gated-sodium-channel-using-polarizable-force-field
#11
Rui-Ning Sun, Haipeng Gong
Voltage-gated sodium (NaV) channels play vital roles in the signal transduction of excitable cells. Upon activation of a NaV channel, the change of transmembrane voltage triggers conformational change of the voltage sensing domain, which then elicits opening of the pore domain and thus allows an influx of Na(+) ions. Description of this process with atomistic details is in urgent demand. In this work, we simulated the partial activation process of the voltage sensing domain of a prokaryotic NaV channel using a polarizable force field...
February 9, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28155939/proposal-of-a-new-mechanism-for-the-directional-propagation-of-the-action-potential-using-a-mimicking-system
#12
Y Takano, O Shirai, Y Kitazumi, K Kano
A nerve conduction model is constructed by using some liquid-membrane cells that mimic the function of the K(+) and Na(+) channels. By imitating two types of Na(+) channels (ligand-gated Na(+) channels and voltage-gated Na(+) channels), a new mechanism for the directional propagation of the action potential along the axon toward the axon terminal is proposed. When the nerve cell is excited by an external (outer) stimulus, it can be presumed that the ligand-gated channels work as power sources at the synapse to propagate the change in the membrane potential, and then the voltage-gated channels locally assist the propagation at each site of the axon (nodes of Ranvier)...
February 3, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28150887/differential-effects-of-energy-deprivation-on-intracellular-sodium-homeostasis-in-neurons-and-astrocytes
#13
REVIEW
Niklas J Gerkau, Cordula Rakers, Gabor C Petzold, Christine R Rose
The maintenance of a low intracellular sodium concentration by the Na(+) /K(+) -ATPase (NKA) is critical for brain function. In both neurons and glial cells, NKA activity is required to counteract changes in the sodium gradient due to opening of voltage- and ligand-gated channels and/or activation of sodium-dependent secondary active transporters. Because NKA consumes about 50% of cellular ATP, sodium homeostasis is strictly dependent on an intact cellular energy metabolism. Despite the high energetic costs of electrical signaling, neurons do not contain significant energy stores themselves, but rely on a close metabolic interaction with surrounding astrocytes...
February 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28141971/paracrine-maturation-and-migration-of-sh-sy5y-cells-by-dental-pulp-stem-cells
#14
P Gervois, E Wolfs, Y Dillen, P Hilkens, J Ratajczak, R B Driesen, T Vangansewinkel, A Bronckaers, B Brône, T Struys, I Lambrichts
Neurological disorders are characterized by neurodegeneration and/or loss of neuronal function, which cannot be adequately repaired by the host. Therefore, there is need for novel treatment options such as cell-based therapies that aim to salvage or reconstitute the lost tissue or that stimulate host repair. The present study aimed to evaluate the paracrine effects of human dental pulp stem cells (hDPSCs) on the migration and neural maturation of human SH-SY5Y neuroblastoma cells. The hDPSC secretome had a significant chemoattractive effect on SH-SY5Y cells as shown by a transwell assay...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28119060/conditional-knockout-of-fgf13-in-murine-hearts-increases-arrhythmia-susceptibility-and-reveals-novel-ion-channel-modulatory-roles
#15
Xiangchong Wang, He Tang, Eric Q Wei, Zhihua Wang, Jing Yang, Rong Yang, Sheng Wang, Yongjian Zhang, Geoffrey S Pitt, Hailin Zhang, Chuan Wang
The intracellular fibroblast growth factors (iFGF/FHFs) bind directly to cardiac voltage gated Na(+) channels, and modulate their function. Mutations that affect iFGF/FHF-Na(+) channel interaction are associated with arrhythmia syndromes. Although suspected to modulate other ionic currents, such as Ca(2+) channels based on acute knockdown experiments in isolated cardiomyocytes, the in vivo consequences of iFGF/FHF gene ablation on cardiac electrical activity are still unknown. We generated inducible, cardiomyocyte-restricted Fgf13 knockout mice to determine the resultant effects of Fgf13 gene ablation...
January 21, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28118359/the-ampk-activator-a769662-blocks-voltage-gated-sodium-channels-discovery-of-a-novel-pharmacophore-with-potential-utility-for-analgesic-development
#16
Marina N Asiedu, Chongyang Han, Sulayman D Dib-Hajj, Stephen G Waxman, Theodore J Price, Gregory Dussor
Voltage-gated sodium channels (VGSC) regulate neuronal excitability by governing action potential (AP) generation and propagation. Recent studies have revealed that AMP-activated protein kinase (AMPK) activators decrease sensory neuron excitability, potentially by preventing sodium (Na+) channel phosphorylation by kinases such as ERK or via modulation of translation regulation pathways. The direct positive allosteric modulator A769662 displays substantially greater efficacy than other AMPK activators in decreasing sensory neuron excitability suggesting additional mechanisms of action...
2017: PloS One
https://www.readbyqxmd.com/read/28116246/logistic-regression-analysis-of-populations-of-electrophysiological-models-to-assess-proarrythmic-risk
#17
Stefano Morotti, Eleonora Grandi
Population-based computational approaches have been developed in recent years and helped to gain insight into arrhythmia mechanisms, and intra- and inter-patient variability (e.g., in drug responses). Here, we illustrate the use of multivariable logistic regression to analyze the factors that enhance or reduce the susceptibility to cellular arrhythmogenic events. As an example, we generate 1000 model variants by randomly modifying ionic conductances and maximal rates of ion transports in our atrial myocyte model and simulate an arrhythmia-provoking protocol that enhances early afterdepolarization (EAD) proclivity...
2017: MethodsX
https://www.readbyqxmd.com/read/28114421/immediate-effects-of-repetitive-magnetic-stimulation-on-single-cortical-pyramidal-neurons
#18
Jineta Banerjee, Mary E Sorrell, Pablo A Celnik, Galit Pelled
Repetitive Transcranial Magnetic Stimulation (rTMS) has been successfully used as a non-invasive therapeutic intervention for several neurological disorders in the clinic as well as an investigative tool for basic neuroscience. rTMS has been shown to induce long-term changes in neuronal circuits in vivo. Such long-term effects of rTMS have been investigated using behavioral, imaging, electrophysiological, and molecular approaches, but there is limited understanding of the immediate effects of TMS on neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28109880/dynamics-of-the-eag1-k-channel-selectivity-filter-assessed-by-molecular-dynamics-simulations
#19
Harald Bernsteiner, Michael Bründl, Anna Stary-Weinzinger
EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4...
January 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28103733/essential-oil-composition-and-antinociceptive-activity-of-thymus-capitatus
#20
Juan Carlos Ramos Gonçalves, Danilo Andrade de Meneses, Aliny Pereira de Vasconcelos, Celyane Alves Piauilino, Fernanda Regina de Castro Almeida, Edoardo Marco Napoli, Giuseppe Ruberto, Demetrius Antônio Machado de Araújo
CONTEXT: The essential oil (EO) from Thymus capitatus Hoff. et Link. (Lamiaceae) has been traditionally used for its medicinal properties, such as anti-inflammatory, analgesic, antioxidant and antimicrobial properties. OBJECTIVE: Characterize the constituents from T. capitatus EO and further evaluate the antinociceptive activity by in vivo and in vitro procedures. MATERIALS AND METHODS: Gas chromatography-mass spectrometry was used to identify and quantify the constituents of the T...
December 2017: Pharmaceutical Biology
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