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voltage-gated Na channel

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https://www.readbyqxmd.com/read/28522250/ppargamma-agonists-rescue-increased-phosphorylation-of-fgf14-at-s226-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#1
Wei-Chun J Hsu, Norelle C Wildburger, Sigmund J Haidacher, Miroslav N Nenov, Oluwarotimi Folorunso, Aditya K Singh, Brent C Chesson, Whitney F Franklin, Ibdanelo Cortez, Rovshan G Sadygov, Kelly T Dineley, Jay S Rudra, Giulio Taglialatela, Cheryl F Lichti, Larry Denner, Fernanda Laezza
BACKGROUND: Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation...
May 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28514017/isopimaric-acid-a-multi-targeting-ion-channel-modulator-reducing-excitability-and-arrhythmicity-in-a-spontaneously-beating-mouse-atrial-cell-line
#2
Sajjad Salari, Malin Silverå Ejneby, Johan Brask, Fredrik Elinder
AIM: Atrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. METHODS: Spontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. RESULTS: 1-25 μmol L(-1) IPA reduced the action potential frequency by up to 50%...
May 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28508747/voltage-gated-na-currents-in-human-dorsal-root-ganglion-neurons
#3
Xiulin Zhang, Birgit T Priest, Inna Belfer, Michael S Gold
Available evidence indicates voltage-gated Na(+) channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons...
May 16, 2017: ELife
https://www.readbyqxmd.com/read/28507035/long-term-sensitization-training-in-aplysia-decreases-the-excitability-of-a-decision-making-neuron-through-a-sodium-dependent-mechanism
#4
John S Hernandez, Marcy L Wainwright, Riccardo Mozzachiodi
In Aplysia, long-term sensitization (LTS) occurs concurrently with a suppression of feeding. At the cellular level, the suppression of feeding is accompanied by decreased excitability of decision-making neuron B51. We examined the contribution of voltage-gated Na(+) and K(+) channels to B51 decreased excitability. In a pharmacologically isolated Na(+) channels environment, LTS training significantly increased B51 firing threshold, compared with untrained controls. Conversely, in a pharmacologically isolated K(+) channels environment, no differences were observed between trained and untrained animals in either amplitude or area of B51 K(+)-dependent depolarizations...
June 2017: Learning & Memory
https://www.readbyqxmd.com/read/28497254/9-phenanthrol-modulates-postinhibitory-rebound-and-afterhyperpolarizing-potentials-in-an-excitatory-motor-neuron-of-the-medicinal-leech
#5
James D Angstadt, Joshua R Giordano, Alexander J Goncalves
Postinhibitory rebound (PIR) responses in leech dorsal excitatory motor neurons (cell DE-3) are eliminated by Ca(2+) channel blockers but also exhibit a strong dependence on extracellular Na(+). These features could be explained by a voltage-gated Ca(2+) current acting in concert with a Ca(2+)-activated nonspecific current (ICAN). In vertebrates, ICAN is associated with TRPM4 channels which are blocked selectively by 9-phenanthrol. Here, we show that 9-phenanthrol selectively inhibits a late phase of PIR and simultaneously enhances afterhyperpolarizing potentials (AHPs)...
May 11, 2017: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/28482835/mechanism-of-resveratrol-induced-relaxation-in-the-human-gallbladder
#6
Ching-Chung Tsai, Ming-Che Lee, Shu-Leei Tey, Ching-Wen Liu, Shih-Che Huang
BACKGROUND: Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips...
May 8, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28472842/diterpene-lipo-alkaloids-with-selective-activities-on-cardiac-k-channels
#7
Tivadar Kiss, Botond Borcsa, Péter Orvos, László Tálosi, Judit Hohmann, Dezső Csupor
Aconitum diterpene alkaloids are known for their remarkable toxicity, which is due to their effect on ion channels. Activation of voltage-gated Na(+) channels is the major cause of their cardiotoxicity, however, influence on K(+) channels may also play a role in the overall effect.Here we report the synthesis of a series of lipo-alkaloids, including four new compounds, based on the 14-benzoylaconine structure, which is the core of a vast number of diterpene alkaloids naturally occurring in Aconitum species...
May 4, 2017: Planta Medica
https://www.readbyqxmd.com/read/28469558/intracellular-fibroblast-growth-factor-14-emerging-risk-factor-for-brain-disorders
#8
REVIEW
Jessica Di Re, Paul A Wadsworth, Fernanda Laezza
The finely tuned regulation of neuronal firing relies on the integrity of ion channel macromolecular complexes. Minimal disturbances of these tightly regulated networks can lead to persistent maladaptive plasticity of brain circuitry. The intracellular fibroblast growth factor 14 (FGF14) belongs to the nexus of proteins interacting with voltage-gated Na+ (Nav) channels at the axonal initial segment. Through isoform-specific interactions with the intracellular C-terminal tail of neuronal Nav channels (Nav1.1, Nav1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28466490/local-and-regional-control-of-calcium-dynamics-in-the-pancreatic-islet
#9
REVIEW
Guy A Rutter, David J Hodson, Pauline Chabosseau, Elizabeth Haythorne, Timothy J Pullen, Isabelle Leclerc
Ca(2+) is the key intracellular regulator of insulin secretion, acting in the beta cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K(+) channel closure and plasma membrane depolarisation engage a sophisticated machinery to drive pulsatile cytosolic Ca(2+) changes. Voltage-gated Ca(2+) channels, Ca(2+) -activated K(+) channels and Na(+) /Ca(2+) exchange all play important roles. The use of targeted Ca(2+) probes has revealed that during each cytosolic Ca(2+) pulse, uptake of Ca(2+) by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca(2+) dynamics and control organellar function...
May 3, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28461495/inducible-fgf13-ablation-enhances-caveolae-mediated-cardioprotection-during-cardiac-pressure-overload
#10
Eric Q Wei, Daniel S Sinden, Lan Mao, Hailin Zhang, Chuan Wang, Geoffrey S Pitt
The fibroblast growth factor (FGF) homologous factor FGF13, a noncanonical FGF, has been best characterized as a voltage-gated Na(+) channel auxiliary subunit. Other cellular functions have been suggested, but not explored. In inducible, cardiac-specific Fgf13 knockout mice, we found-even in the context of the expected reduction in Na(+) channel current-an unanticipated protection from the maladaptive hypertrophic response to pressure overload. To uncover the underlying mechanisms, we searched for components of the FGF13 interactome in cardiomyocytes and discovered the complete set of the cavin family of caveolar coat proteins...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28433711/mdh2-is-an-rna-binding-protein-involved-in-downregulation-of-sodium-channel-scn1a-expression-under-seizure-condition
#11
Yong-Hong Chen, Shu-Jing Liu, Mei-Mei Gao, Tao Zeng, Guo-Wang Lin, Na-Na Tan, Hui-Ling Tang, Ping Lu, Tao Su, Wei-Wen Sun, Long-Chang Xie, Yong-Hong Yi, Yue-Sheng Long
Voltage-gated sodium channel α-subunit type I (NaV1.1, encoded by SCN1A gene) plays a critical role in the excitability of brain. Downregulation of SCN1A expression is associated with epilepsy, a common neurological disorder characterized by recurrent seizures. Here we reveal a novel role of malate dehydrogenase 2 (MDH2) in the posttranscriptional regulation of SCN1A expression under seizure condition. We identified that MDH2 was an RNA binding protein that could bind two of the four conserved regions in the 3' UTRs of SCN1A...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28424991/expression-and-role-of-voltage-gated-sodium-channels-in-human-dorsal-root-ganglion-neurons-with-special-focus-on-nav1-7-species-differences-and-regulation-by-paclitaxel
#12
Wonseok Chang, Temugin Berta, Yong Ho Kim, Sanghoon Lee, Seok-Yong Lee, Ru-Rong Ji
Voltage-gated sodium channels (Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion (hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Nav1.7 (~50% of total Nav expression) and lower expression of Nav1.8 (~12%), whereas the mouse DRG has higher expression of Nav1.8 (~45%) and lower expression of Nav1...
April 19, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28423317/loss-of-nav%C3%AE-4-mediated-regulation-of-sodium-currents-in-adult-purkinje-neurons-disrupts-firing-and-impairs-motor-coordination-and-balance
#13
Joseph L Ransdell, Edward Dranoff, Brandon Lau, Wan-Lin Lo, David L Donermeyer, Paul M Allen, Jeanne M Nerbonne
The resurgent component of voltage-gated Na(+) (Nav) currents, INaR, has been suggested to provide the depolarizing drive for high-frequency firing and to be generated by voltage-dependent Nav channel block (at depolarized potentials) and unblock (at hyperpolarized potentials) by the accessory Navβ4 subunit. To test these hypotheses, we examined the effects of the targeted deletion of Scn4b (Navβ4) on INaR and on repetitive firing in cerebellar Purkinje neurons. We show here that Scn4b(-/-) animals have deficits in motor coordination and balance and that firing rates in Scn4b(-/-) Purkinje neurons are markedly attenuated...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28423185/functional-identification-of-activity-regulated-high-affinity-glutamine-transport-in-hippocampal-neurons-inhibited-by-riluzole
#14
Jeffrey D Erickson
Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC50 1.3 +/- 0.5μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K(+) -stimulated MeAIB transport displays an affinity (Km ) for MeAIB of 37 +/- 1...
April 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28416648/isoflurane-modulates-activation-and-inactivation-gating-of-the-prokaryotic-na-channel-nachbac
#15
Rheanna M Sand, Kevin J Gingrich, Tamar Macharadze, Karl F Herold, Hugh C Hemmings
Voltage-gated Na(+) channels (Nav) have emerged as important presynaptic targets for volatile anesthetic (VA) effects on synaptic transmission. However, the detailed biophysical mechanisms by which VAs modulate Nav function remain unclear. VAs alter macroscopic activation and inactivation of the prokaryotic Na(+) channel, NaChBac, which provides a useful structural and functional model of mammalian Nav Here, we study the effects of the common general anesthetic isoflurane on NaChBac function by analyzing macroscopic Na(+) currents (INa) in wild-type (WT) channels and mutants with impaired (G229A) or enhanced (G219A) inactivation...
April 17, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28408211/cardiac-voltage-gated-ion-channels-in-safety-pharmacology-review-of-the-landscape-leading-to-the-cipa-initiative
#16
REVIEW
Hai Huang, Michael K Pugsley, Bernard Fermini, Michael J Curtis, John Koerner, Michael Accardi, Simon Authier
Voltage gated ion channels are central in defining the fundamental properties of the ventricular cardiac action potential (AP), and are also involved in the development of drug-induced arrhythmias. Many drugs can inhibit cardiac ion currents, including the Na(+) current (INa), L-type Ca(2+) current (Ica-L), and K(+) currents (Ito, IK1, IKs, and IKr), and thereby affect AP properties in a manner that can trigger or sustain cardiac arrhythmias. Since publication of ICH E14 and S7B over a decade ago, there has been a focus on drug effects on QT prolongation clinically, and on the rapidly activating delayed rectifier current (IKr), nonclinically, for evaluation of proarrhythmic risk...
April 11, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28406893/the-chemical-basis-for-electrical-signaling
#17
REVIEW
William A Catterall, Goragot Wisedchaisri, Ning Zheng
Electrical signals generated by minute currents of ions moving across cell membranes are central to all rapid processes in biology. Initiation and propagation of electrical signals requires voltage-gated sodium (NaV) and calcium (CaV) channels. These channels contain a tetramer of membrane-bound subunits or domains comprising a voltage sensor and a pore module. Voltage-dependent activation occurs as membrane depolarization drives outward movements of positive gating changes in the voltage sensor via a sliding-helix mechanism, which leads to a conformational change in the pore module that opens its intracellular activation gate...
April 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28402882/gating-charge-calculations-by-computational-electrophysiology-simulations
#18
Jan-Philipp Machtens, Rodolfo Briones, Claudia Alleva, Bert L de Groot, Christoph Fahlke
Electrical cell signaling requires adjustment of ion channel, receptor, or transporter function in response to changes in membrane potential. For the majority of such membrane proteins, the molecular details of voltage sensing remain insufficiently understood. Here, we present a molecular dynamics simulation-based method to determine the underlying charge movement across the membrane-the gating charge-by measuring electrical capacitor properties of membrane-embedded proteins. We illustrate the approach by calculating the charge transfer upon membrane insertion of the HIV gp41 fusion peptide, and validate the method on two prototypical voltage-dependent proteins, the Kv1...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28394849/inhibition-of-voltage-gated-na-channels-by-bupivacaine-is-enhanced-by-the-adjuvants-buprenorphine-ketamine-and-clonidine
#19
Carsten Stoetzer, Christine Martell, Jeanne de la Roche, Andreas Leffler
BACKGROUND AND OBJECTIVES: Regional anesthesia includes application of local anesthetics (LAs) into the vicinity of peripheral nerves. Prolongation or improvement of nerve blocks with LAs can be accomplished by coapplication with adjuvants, including buprenorphine, ketamine, and clonidine. While the mechanisms mediating prolonged or improved LA-induced effects by adjuvants are poorly understood, we hypothesized that they are likely to increase LA-induced block of voltage-gated Na channels...
April 7, 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28385801/mechanisms-controlling-glucose-induced-glp-1-secretion-in-human-small-intestine
#20
Emily W Sun, Dayan de Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven L Due, David A Wattchow, Christopher K Rayner, Adam M Deane, Richard L Young, Damien J Keating
Intestinal glucose stimulates secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). The mechanisms underlying this pathway have not been fully investigated in humans. In this study, we showed that a 30 minute intraduodenal glucose infusion activated half of all duodenal L cells in humans. This infusion was sufficient to increase plasma GLP-1. With an ex vivo model using human gut tissue specimens, we showed a dose-responsive GLP-1 secretion in ileum at 200mM glucose or above. In ex vivo tissue from duodenum and ileum, but not colon, 300mM glucose potently stimulated GLP-1 release...
April 6, 2017: Diabetes
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