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voltage-gated Na channel

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https://www.readbyqxmd.com/read/28943231/active-mechanisms-of-vibration-encoding-and-frequency-filtering-in-central-mechanosensory-neurons
#1
Anthony W Azevedo, Rachel I Wilson
To better understand biophysical mechanisms of mechanosensory processing, we investigated two cell types in the Drosophila brain (A2 and B1 cells) that are postsynaptic to antennal vibration receptors. A2 cells receive excitatory synaptic currents in response to both directions of movement: thus, twice per vibration cycle. The membrane acts as a low-pass filter, so that voltage and spiking mainly track the vibration envelope rather than individual cycles. By contrast, B1 cells are excited by only forward or backward movement, meaning they are sensitive to vibration phase...
September 19, 2017: Neuron
https://www.readbyqxmd.com/read/28939972/effects-of-benzothiazolamines-on-voltage-gated-sodium-channels
#2
Alessandro Farinato, Concetta Altamura, Jean-François Desaphy
Benzothiazole is a versatile fused heterocycle that aroused much interest in drug discovery as anticonvulsant, neuroprotective, analgesic, anti-inflammatory, antimicrobial, and anticancer. Two benzothiazolamines, riluzole and lubeluzole, are known blockers of voltage-gated sodium (Nav) channels. Riluzole is clinically used as a neuroprotectant in amyotrophic lateral sclerosis. Inhibition of Nav channels by riluzole is voltage-dependent due to preferential binding to inactivated sodium channels. Yet the drug exerts little use-dependent block, probably because it lacks protonable amine...
September 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28939386/investigation-into-the-role-of-an-extracellular-loop-in-mediating-proton-evoked-inhibition-of-voltage-gated-sodium-channels
#3
Elisa Harms, Carsten Stoetzer, Thomas Stueber, Andrias O O'Reilly, Andreas Leffler
Proton-evoked activation of sensory neurons is counteracted by inhibition of voltage-gated Na(+) channels, and the low acid-sensitivity of sensory neuron of the African naked mole-rat (ANMr) was reported to be due to a strong proton-evoked block of ANMrNav1.7. Here we aimed to reevaluate the role of the suggested negatively-charged motif in the ANMrNav1.7 domain IV P-loop for inhibition by protons. Patch clamp recordings were performed on the recombinant α-subunits Nav1.2-1.8. The insertion of the negatively charged motif (EKE) of ANMrNav1...
September 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28916354/abnormal-sodium-channel-mrna-splicing-in-hypertrophic-cardiomyopathy
#4
Adam M Noyes, Anyu Zhou, Ge Gao, Lianzhi Gu, Sharlene Day, J Andrew Wasserstrom, Samuel C Dudley
BACKGROUND: Our previous studies showed that in ischemic and nonischemic heart failure (HF), the voltage-gated cardiac Na(+) channel α subunit (SCN5A) mRNA is abnormally spliced to produce two truncated transcript variants (E28C and D) that activate the unfolded protein response (UPR). We tested whether SCN5A post-transcriptional regulation was abnormal in hypertrophic cardiomyopathy (HCM). MATERIAL AND METHODS: Human heart tissue was obtained from HCM patients...
September 7, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28915149/bulleyaconitine-a-preferably-reduces-tetrodotoxin-sensitive-sodium-current-in-uninjured-dorsal-root-ganglion-neurons-of-neuropathic-rats-probably-via-inhibition-of-protein-kinase-c
#5
Man-Xiu Xie, Rui-Ping Pang, Jie Yang, Kai-Feng Shen, Jing Xu, Xiong-Xiong Zhong, Shao-Kun Wang, Xiao-Long Zhang, Yan-Qing Liu, Xian-Guo Liu
Oral Bulleyaconitine A (BLA) is effective for treating neuropathic pain in human patients, but the underlying mechanism is poorly understood. Here, we tested whether BLA blocked voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons. Compelling evidence shows that voltage-gated sodium channels are upregulated in uninjured DRG neurons but downregulated in injured ones following peripheral nerve injury. We found that BLA preferably inhibited Na currents in uninjured DRG neurons in neuropathic rats...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28904093/sodium-dynamics-in-pyramidal-neuron-dendritic-spines-synaptically-evoked-entry-predominantly-through-ampa-receptors-and-removal-by-diffusion
#6
Kenichi Miyazaki, William N Ross
Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties with newly developed simultaneous sodium and calcium imaging that had single spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high speed, low noise CCD camera...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28882890/c-terminal-phosphorylation-of-nav1-5-impairs-fgf13-dependent-regulation-of-channel-inactivation
#7
Sophie Burel, Fabien C Coyan, Maxime Lorenzini, Matthew R Meyer, Cheryl F Lichti, Joan H Brown, Gildas Loussouarn, Flavien Charpentier, Jeanne M Nerbonne, R Reid Townsend, Lars S Maier, Céline Marionneau
Voltage-gated Na(+) (NaV) channels are key regulators of myocardial excitability, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent alterations in NaV1.5 channel inactivation are emerging as a critical determinant of arrhythmias in heart failure. However, the global native phosphorylation pattern of NaV1.5 subunits associated with these arrhythmogenic disorders, and the associated channel regulatory defects remain unknown. Here, we undertook phosphoproteomic analyses to identify and quantify in situ the phosphorylation sites in the NaV1...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28878030/the-hyperpolarization-activated-cyclic-nucleotide-gated-channels-from-biophysics-to-pharmacology-of-a-unique-family-of-ion-channels
#8
REVIEW
Laura Sartiani, Guido Mannaioni, Alessio Masi, Maria Novella Romanelli, Elisabetta Cerbai
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important members of the voltage-gated pore loop channels family. They show unique features: they open at hyperpolarizing potential, carry a mixed Na/K current, and are regulated by cyclic nucleotides. Four different isoforms have been cloned (HCN1-4) that can assemble to form homo- or heterotetramers, characterized by different biophysical properties. These proteins are widely distributed throughout the body and involved in different physiologic processes, the most important being the generation of spontaneous electrical activity in the heart and the regulation of synaptic transmission in the brain...
October 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28874544/single-rat-muscle-na-channel-mutation-confers-batrachotoxin-autoresistance-found-in-poison-dart-frog-phyllobates-terribilis
#9
Sho-Ya Wang, Ging Kuo Wang
Poison-dart Phyllobates terribilis frogs sequester lethal amounts of steroidal alkaloid batrachotoxin (BTX) in their skin as a defense mechanism against predators. BTX targets voltage-gated Na(+) channels and enables them to open persistently. How BTX autoresistance arises in such frogs remains a mystery. The BTX receptor has been delineated along the Na(+) channel inner cavity, which is formed jointly by four S6 transmembrane segments from domains D1 to D4. Within the P. terribilis muscle Na(+) channel, five amino acid (AA) substitutions have been identified at D1/S6 and D4/S6...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28871036/sodium-channel-%C3%AE-2-subunits-prevent-action-potential-propagation-failures-at-axonal-branch-points
#10
In Ha Cho, Lauren C Panzera, Morven Chin, Michael B Hoppa
Neurotransmitter release depends on voltage-gated Na(+) channels (Navs) to successfully propagate an action potential (AP) from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na(+) channels. Using optical recordings of Ca(2+) and membrane voltage, we demonstrate that Na(+) channel β2 subunits (Navβ2) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female)...
September 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28837387/crmp2-is-necessary-for-neurofibromatosis-type-1-related-pain
#11
Aubin Moutal, Song Cai, Shizhen Luo, Raphaëlle Voisin, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases, affecting roughly 1 in 3000 individuals. As a multisystem disorder, it affects cognitive development, as well as bone, nerve and muscle constitution. Peripheral neuropathy in NF1 constitutes a potentially severe clinical complication and is associated with increased morbidity and mortality. The discovery of effective therapies for Neurofibromatosis type 1 (NF1) pain depends on mechanistic understanding that has been limited, in part, by the relative lack of availability of animal models relevant to NF1 pain...
August 24, 2017: Channels
https://www.readbyqxmd.com/read/28826537/actions-and-regulation-of-ionotropic-cannabinoid-receptors
#12
Luciano De Petrocellis, Massimo Nabissi, Giorgio Santoni, Alessia Ligresti
Almost three decades have passed since the identification of the two specific metabotropic receptors mediating cannabinoid pharmacology. Thereafter, many cannabinoid effects, both at central and peripheral levels, have been well documented and characterized. However, numerous evidences demonstrated that these pharmacological actions could not be attributable solely to the activation of CB1 and CB2 receptors since several important cannabimimetic actions have been found in biological systems lacking CB1 or CB2 gene such as in specific cell lines or transgenic mice...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28822854/involvement-of-cyclic-nucleotide-gated-channels-in-spontaneous-activity-generated-in-isolated-interstitial-cells-of-cajal-from-the-rabbit-urethra
#13
Maria Sancho, Eamonn Bradley, Angeles Garcia-Pascual, Domingo Triguero, Keith D Thornbury, Mark A Hollywood, Gerard P Sergeant
Cyclic nucleotide-gated (CNG) channels are non-selective cation channels that mediate influx of extracellular Na(+) and Ca(2+) in various cell types. L-cis-Diltiazem, a CNG channel blocker, inhibits contraction of urethral smooth muscle (USM), however the mechanisms underlying this effect are still unclear. We investigated the possibility that CNG channels contribute to spontaneous pacemaker activity in freshly isolated interstitial cells of Cajal (ICC) isolated from the rabbit urethra (RUICC). Using immunocytochemistry, we found intense CNG1-immunoreactivity in vimentin-immunoreactive RUICC, mainly within patches of the cellular body and processes...
August 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28782435/rufinamide-pretreatment-attenuates-ischemia-reperfusion-injury-in-the-gerbil-hippocampus
#14
Chan Woo Park, Tae-Kyeong Lee, Jeong Hwi Cho, In Hye Kim, Jae-Chul Lee, Bich-Na Shin, Ji Hyeon Ahn, Sung Koo Kim, Myoung Cheol Shin, Taek Geun Ohk, Jun Hwi Cho, Moo-Ho Won, Young Joo Lee, Jeong Yeol Seo, Joon Ha Park
OBJECTIVES: Rufinamide, a voltage-gated sodium channel (VGSC) blocker, is widely used for the clinical treatment of seizures associated with Lennox-Gastaut syndrome. Previous studies have demonstrated that VGSC blockers have neuroprotective properties against ischemic damage following experimental cerebral ischemia. However, protective effects of rufinamide against cerebral ischemic insults have not been addressed. Therefore, in the present study, we firstly examined neuroprotective effects of rufinamide using a gerbil model of transient global cerebral ischemia...
August 7, 2017: Neurological Research
https://www.readbyqxmd.com/read/28758202/sodium-channel-subtypes-are-differentially-localized-to-pre-and-post-synaptic-sites-in-rat-hippocampus
#15
Kenneth W Johnson, Karl F Herold, Teresa A Milner, Hugh C Hemmings, Jimcy Platholi
Voltage-gated Na(+) channels (Nav ) modulate neuronal excitability, but the roles of the various Nav subtypes in specific neuronal functions such as synaptic transmission are unclear. We investigated expression of the three major brain Nav subtypes (Nav 1.1, Nav 1.2, Nav 1.6) in area CA1 and dentate gyrus of rat hippocampus. Using light and electron microscopy, we found labeling for all three Nav subtypes on dendrites, dendritic spines, and axon terminals, but the proportion of pre- and post-synaptic labeling for each subtype varied within and between subregions of CA1 and dentate gyrus...
July 31, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28727929/na-h-exchanger-and-proton-channel-in-heart-failure-associated-with-becker-and-duchenne-muscular-dystrophies
#16
Ghassan Bkaily, Danielle Jacques
Cardiomyopathy is found in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, which are linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects are not limited to DMD but are also present in mild BMD. The hereditary cardiomyopathic hamster of the UM-X7.1 strain is a particular experimental model of heart failure (HF) leading to early death in muscular dystrophy (dystrophin deficiency and sarcoglycan mutation) and heart disease (δ-sarcoglycan deficiency and dystrophin mutation) in human DMD...
July 20, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28720590/mechanisms-of-noncovalent-%C3%AE-subunit-regulation-of-nav-channel-gating
#17
Wandi Zhu, Taylor L Voelker, Zoltan Varga, Angela R Schubert, Jeanne M Nerbonne, Jonathan R Silva
Voltage-gated Na(+) (NaV) channels comprise a macromolecular complex whose components tailor channel function. Key components are the non-covalently bound β1 and β3 subunits that regulate channel gating, expression, and pharmacology. Here, we probe the molecular basis of this regulation by applying voltage clamp fluorometry to measure how the β subunits affect the conformational dynamics of the cardiac NaV channel (NaV1.5) voltage-sensing domains (VSDs). The pore-forming NaV1.5 α subunit contains four domains (DI-DIV), each with a VSD...
July 18, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28715135/chronic-pharmacological-blockade-of-the-na-ca-2-exchanger-modulates-the-growth-and-development-of-the-purkinje-cell-dendritic-arbor-in-mouse-cerebellar-slice-cultures
#18
Pradeep Sherkhane, Josef P Kapfhammer
The Na(+) /Ca(2+) exchanger (NCX) is a bidirectional plasma membrane antiporter involved in Ca(2+) homeostasis in eukaryotes. NCX has three isoforms, NCX1-3, and all of them are expressed in the cerebellum. Immunostaining on cerebellar slice cultures indicates that NCX is widely expressed in the cerebellum, including expression in Purkinje cells. The pharmacological blockade of the forward mode of NCX (Ca(2+) efflux mode) by bepridil moderately inhibited growth and development of Purkinje cell dendritic arbor in cerebellar slice cultures...
July 17, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28709814/the-therapeutic-implication-of-a-novel-scn2a-mutation-associated-early-onset-epileptic-encephalopathy-with-rett-like-features
#19
Jao-Shwann Liang, Li-Ju Lin, Ming-Tao Yang, Jinn-Shyan Wang, Jyh-Feng Lu
Epileptic encephalopathies are highly heterogeneous and phenotypical disorders with different underlying genetic defects. Mutations in the SCN2A gene cause different epilepsy syndromes, including epilepsy of infancy with migrating focal seizures, Ohtahara syndrome, and West syndrome. We utilized a targeted next generation sequencing (NGS) approach on a girl with early-onset seizures and Rett-like features, including autistic behavior, limited hand function with chorea, and profound intellectual disability, to identify novel missense mutation (c...
July 11, 2017: Brain & Development
https://www.readbyqxmd.com/read/28705737/leptin-regulation-of-inward-membrane-currents-electrical-activity-and-lh-release-in-isolated-bovine-gonadotropes
#20
Belisario Domínguez-Mancera, Manuel Barrientos-Morales, Patricia Cervantes-Acosta, Antonio Hernández-Beltrán, Araceli Rodríguez-Andrade, Ricardo González-Ramírez, Eduardo Monjaraz, Ricardo Felix
Leptin, a peptide hormone produced by adipocytes, is recognized as one of the signals involved in the onset of reproductive activity. The leptin receptor has been found in hypothalamic neurons and pituitary gonadotropes, suggesting that the hormone may act at both sites to stimulate the secretion of GnRH and consequently, FSH and LH. In response to a stimulus such as a hypothalamic secretagogue, gonadotropes respond with changes in electrical activity, intracellular Ca(2+) and hormone release. The main aim of this report was to investigate whether leptin promotes a change in the electrical and secretory activities of bovine gonadotropes...
September 9, 2017: Biochemical and Biophysical Research Communications
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