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https://www.readbyqxmd.com/read/29318638/voltage-gated-sodium-channels-nav-igating-the-field-to-determine-their-contribution-to-visceral-nociception
#1
Andelain Erickson, Annemie Deiteren, Andrea M Harrington, Sonia Garcia-Caraballo, Joel Castro, Ashlee Caldwell, Luke Grundy, Stuart M Brierley
Chronic visceral pain, altered motility and bladder dysfunction are common, yet poorly managed symptoms of functional and inflammatory disorders of the gastrointestinal and urinary tracts. Recently, numerous human channelopathies of the voltage-gated sodium (NaV ) channel family have been identified, which induce either painful neuropathies, an insensitivity to pain, or alterations in smooth muscle function. The identification of these disorders, in addition to the recent utilisation of genetically modified NaV mice and specific NaV channel modulators, has shed new light on how NaV channels contribute to the function of neuronal and non-neuronal tissues within the gastrointestinal tract and bladder...
January 9, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29248843/modulation-of-voltage-gated-sodium-channels-induces-capacitation-in-bull-spermatozoa-through-phosphorylation-of-tyrosine-containing-proteins
#2
Dharmendra Singh Chauhan, Dilip Kumar Swain, Nadeem Shah, Hanuman Prasad Yadav, Abhishek Sharma, Brijesh Yadav, Sarvajeet Yadav, Rajesh Nigam, Satish Kumar Garg
In our previous study, we have reported the molecular presence of Nav 1.8 in bull spermatozoa and its potential involvement in regulation of sperm functions. With the selective blocking of Nav 1.8 using A-803467, alterations in sperm functions were observed, therefore, we envisaged of investigating the involvement of Nav in regulating sperm function and the mechanism(s) involved in it using veratridine, a selective opener of Nav channels. Forty ejaculates were collected from four Hariana bulls and semen samples were pooled in view of the non-significant variations between the different ejaculates...
November 27, 2017: Theriogenology
https://www.readbyqxmd.com/read/29218789/precise-localizations-of-voltage-gated-sodium-and-potassium-channels-in-neurons
#3
REVIEW
Hiroaki Misonou
Neurons are extremely large and complex cells, and they regulate membrane potentials in multiple subcellular compartments using a variety of ion channels. Voltage-gated sodium (Nav) and potassium (Kv) channels are crucial in regulating neuronal membrane excitability owing to their diversity in subtypes, biophysical properties, and localizations. In particular, specific localizations of Nav and Kv channels in specific membrane compartments are essential to achieve a precise control of local membrane excitability...
December 8, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29210458/distribution-of-cardiac-sodium-channels-in-clusters-potentiates-ephaptic-interactions-in-the-intercalated-disc
#4
Echrak Hichri, Hugues Abriel, Jan P Kucera
It has been proposed that ephaptic interactions in intercalated discs, mediated by extracellular potentials, contribute to cardiac impulse propagation when gap junctional coupling is reduced. However, experiments demonstrating ephaptic effects on the cardiac Na+ current (INa ) are scarce. Furthermore, Na+ channels form clusters around gap junction plaques, but the electrophysiological significance of these clusters has never been investigated. In patch clamp experiments with HEK cells stably expressing human Nav 1...
December 6, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29193176/using-voltage-sensor-toxins-and-their-molecular-targets-to-investigate-nav-1-8-gating
#5
John Gilchrist, Frank Bosmans
Voltage-gated sodium (NaV ) channel gating is a complex phenomenon which involves a distinct contribution of four integral voltage-sensing domains (VSDI, VSDII, VSDIII, and VSDIV). Utilizing accrued pharmacological and structural insights, we build on an established chimera approach to introduce animal toxin sensitivity in each VSD of an acceptor channel by transferring in portable S3b-S4 motifs from the four VSDs of a toxin-susceptible donor channel (NaV 1.2). By doing so, we observe that in NaV 1.8, a relatively unexplored channel subtype with distinctly slow gating kinetics, VSDI-III participate in channel opening whereas VSDIV can regulate opening as well as fast inactivation...
November 29, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29193076/resurgent-sodium-current-promotes-action-potential-firing-in-the-avian-auditory-brainstem
#6
Hui Hong, Ting Lu, Xiaoyu Wang, Yuan Wang, Jason Tait Sanchez
Auditory brainstem neurons are functionally primed to fire action potentials (APs) at markedly high-rates in order to rapidly encode acoustic information of sound. This specialization is critical for survival and the comprehension of behaviourally relevant communication functions, including sound localization and understanding speech in noise. Here, we investigated underlying ion channel mechanisms essential for high-rate AP firing in neurons of the chicken nucleus magnocellularis (NM) - the avian analog of bushy cells of the mammalian anteroventral cochlear nucleus...
November 28, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29190805/single-molecule-study-of-full-length-nachbac-by-planar-lipid-bilayer-recording
#7
Andrew Jo, Hiofan Hoi, Hang Zhou, Manisha Gupta, Carlo D Montemagno
Planar lipid bilayer device, alternatively known as BLM, is a powerful tool to study functional properties of conducting membrane proteins such as ion channels and porins. In this work, we used BLM to study the prokaryotic voltage-gated sodium channel (Nav) NaChBac in a well-defined membrane environment. Navs are an essential component for the generation and propagation of electric signals in excitable cells. The successes in the biochemical, biophysical and crystallographic studies on prokaryotic Navs in recent years has greatly promoted the understanding of the molecular mechanism that underlies these proteins and their eukaryotic counterparts...
2017: PloS One
https://www.readbyqxmd.com/read/29180755/nav-channel-binder-containing-a-specific-conjugation-site-based-on-a-low-toxicity-%C3%AE-scorpion-toxin
#8
Tomoya Kubota, Bobo Dang, Joao L Carvalho-de-Souza, Ana M Correa, Francisco Bezanilla
Voltage-gated sodium (Nav) channels play a key role in generating action potentials which leads to physiological signaling in excitable cells. The availability of probes for functional studies of mammalian Nav is limited. Here, by introducing two amino acid substitutions into the beta scorpion toxin Ts1, we have chemically synthesized a novel binder [S14R, W50Pra]Ts1 for Nav with high affinity, low dissociation rate and reduced toxicity while retaining the capability of conjugating Ts1 with molecules of interests for different applications...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29163198/ankyrins-and-spectrins-in-cardiovascular-biology-and-disease
#9
REVIEW
Mona M El Refaey, Peter J Mohler
Ankyrins are adaptor proteins critical for the expression and targeting of cardiac membrane proteins, signaling molecules, and cytoskeletal elements. Findings in humans and animal models have highlighted the in vivo roles for ankyrins in normal physiology and in cardiovascular disease, most notably in cardiac arrhythmia. For example, human ANK2 loss-of-function variants are associated with a complex array of electrical and structural phenotypes now termed "ankyrin-B syndrome," whereas alterations in the ankyrin-G pathway for Nav channel targeting are associated with human Brugada syndrome...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29161016/selective-voltage-gated-sodium-channel-peptide-toxins-from-animal-venom-pharmacological-probes-and-analgesic-drug-development
#10
Ying Wu, Hui Ma, Fan Zhang, Chun-Lei Zhang, Xiaohan Zou, Zhengyu Cao
Voltage-gated sodium channels (Navs) play critical roles in action potential generation and propagation. Nav channelopathy as well as pathological sensitization contribute to allodynia and hyperalgesia. Recent evidence has demonstrated the significant roles of Nav subtypes (Nav1.3, 1.7, 1.8 and 1.9) in nociceptive transduction and therefore these Navs may represent attractive targets for analgesic drug discovery. Animal toxins are structurally diverse peptides that are highly potent yet selective on ion channel subtypes and therefore representing valuable probes to elucidate the structures, gating properties and cellular functions of ion channels...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29142310/sodium-channel-nav1-3-is-important-for-enterochromaffin-cell-excitability-and-serotonin-release
#11
Peter R Strege, Kaitlyn Knutson, Samuel J Eggers, Joyce H Li, Fan Wang, David Linden, Joseph H Szurszewski, Lorin Milescu, Andrew B Leiter, Gianrico Farrugia, Arthur Beyder
In the gastrointestinal (GI) epithelium, enterochromaffin (EC) cells are enteroendocrine cells responsible for producing >90% of the body's serotonin (5-hydroxytryptamine, 5-HT). However, the molecular mechanisms of EC cell function are poorly understood. Here, we found that EC cells in mouse primary cultures fired spontaneous bursts of action potentials. We examined the repertoire of voltage-gated sodium channels (NaV) in fluorescence-sorted mouse EC cells and found that Scn3a was highly expressed. Scn3a-encoded NaV1...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138838/effects-of-scn9a-gene-modification-on-na-channel-and-the-expression-of-nerve-growth-factor-in-a-rat-model-of-diarrhea%C3%A2-predominant-irritable-bowel-syndrome
#12
Yong-Yan Cai, Chen Li, Zhi-Xin Yan, Na Ma, Fang-Fang Li
The aim of the present study was to identify whether the sodium voltage-gated channel alpha subunit 9 (SCN9A) gene modification is a potential treatment for diarrhea‑predominant irritable bowel syndrome (D‑IBS), via regulating the Na+ channel and the expression of nerve growth factor (NGF). The recombinant adenovirus vector of the SCN9A gene was established, and rat colon cells were isolated for SCN9A gene modification. All subjects were divided into four groups: i) The SCN9A‑modified (D‑IBS rat model implanted with SCN9A‑modified colon cells), ii) negative control (NC; D‑IBS rat model implanted with colon cells without SCN9A gene modification), iii) blank (D‑IBS rat model without any treatment) and iv) normal (normal rats without any treatment)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109270/m-current-inhibition-rapidly-induces-a-unique-ck2-dependent-plasticity-of-the-axon-initial-segment
#13
Jonathan Lezmy, Maya Lipinsky, Yana Khrapunsky, Eti Patrich, Lia Shalom, Asher Peretz, Ilya A Fleidervish, Bernard Attali
Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes in the axon initial segment (AIS), which is pivotal for spike generation. Here, in hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form of AIS plasticity by selectively targeting M-type K(+) channels, which predominantly localize to the AIS and are essential for tuning neuronal excitability. While acute M-current inhibition via cholinergic activation or direct channel block made neurons more excitable, minutes to hours of sustained M-current depression resulted in a gradual reduction in intrinsic excitability...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29101377/a-high-throughput-model-for-investigating-neuronal-function-and-synaptic-transmission-in-cultured-neuronal-networks
#14
Jasmeet K Virdee, Gabriella Saro, Antoine Fouillet, Jeremy Findlay, Filipa Ferreira, Sarah Eversden, Michael J O'Neill, Joanna Wolak, Daniel Ursu
Loss of synapses or alteration of synaptic activity is associated with cognitive impairment observed in a number of psychiatric and neurological disorders, such as schizophrenia and Alzheimer's disease. Therefore successful development of in vitro methods that can investigate synaptic function in a high-throughput format could be highly impactful for neuroscience drug discovery. We present here the development, characterisation and validation of a novel high-throughput in vitro model for assessing neuronal function and synaptic transmission in primary rodent neurons...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29094210/evolutionary-history-of-voltage-gated-sodium-channels
#15
Atsuo Nishino, Yasushi Okamura
Every cell within living organisms actively maintains an intracellular Na(+) concentration that is 10-12 times lower than the extracellular concentration. The cells then utilize this transmembrane Na(+) concentration gradient as a driving force to produce electrical signals, sometimes in the form of action potentials. The protein family comprising voltage-gated sodium channels (NaVs) is essential for such signaling and enables cells to change their status in a regenerative manner and to rapidly communicate with one another...
November 2, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29079725/complementary-mechanisms-for-neurotoxin-resistance-in-a-copepod
#16
Vittoria Roncalli, Petra H Lenz, Matthew C Cieslak, Daniel K Hartline
Toxin resistance is a recurring evolutionary response by predators feeding on toxic prey. These adaptations impact physiological interaction and community ecology. Mechanisms for resistance vary depending on the predator and the nature of the toxin. Potent neurotoxins like tetrodotoxin (TTX) and saxitoxin (STX) that are highly toxic to humans and other vertebrates, target conserved voltage-gated sodium channels (NaV) of nerve and muscle, causing paralysis. The copepod Calanus finmarchicus consumes the STX-producing dinoflagellate, Alexandrium fundyense with no effect on survival...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29077258/whole-exome-sequencing-identifies-a-novel-mutation-of-gpd1l-r189x-associated-with-familial-conduction-disease-and-sudden-death
#17
Hao Huang, Ya-Qin Chen, Liang-Liang Fan, Shuai Guo, Jing-Jing Li, Jie-Yuan Jin, Rong Xiang
Cardiac conduction disease (CCD) is a serious disorder and the leading cause of mortality worldwide. It is characterized by arrhythmia, syncope or even sudden cardiac death caused by the dysfunction of cardiac voltage-gated channel. Previous study has demonstrated that mutations in genes encoding voltage-gated channel and related proteins were the crucial genetic lesion of CCD. In this study, we employed whole-exome sequencing to explore the potential causative genes in a Chinese family with ventricular tachycardia and syncope...
October 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29055053/expression-patterns-of-ion-channels-and-structural-proteins-in-a-multimodal-cell-type-of-the-avian-optic-tectum
#18
Katharina Lischka, Simone Ladel, Harald Luksch, Stefan Weigel
The midbrain is an important subcortical area involved in distinct functions such as multimodal integration, movement initiation, bottom-up and top-down attention. Our group is particularly interested in cellular computation of multisensory integration. We focus on the visual part of the avian midbrain, the optic tectum (TeO, counterpart to mammalian superior colliculus). This area has a layered structure with the great advantage of distinct in- and output regions. In chicken, the TeO is organized in 15 layers where visual input targets the superficial layers while auditory input terminates in deeper layers...
October 21, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29032483/regulation-of-cardiac-voltage-gated-sodium-channel-by-kinases-roles-of-protein-kinases-a-and-c
#19
Ademuyiwa S Aromolaran, Mohamed Chahine, Mohamed Boutjdir
In the heart, voltage-gated sodium (Nav) channel (Nav1.5) is defined by its pore-forming α-subunit and its auxiliary β-subunits, both of which are important for its critical contribution to the initiation and maintenance of the cardiac action potential (AP) that underlie normal heart rhythm. The physiological relevance of Nav1.5 is further marked by the fact that inherited or congenital mutations in Nav1.5 channel gene SCN5A lead to altered functional expression (including expression, trafficking, and current density), and are generally manifested in the form of distinct cardiac arrhythmic events, epilepsy, neuropathic pain, migraine, and neuromuscular disorders...
October 15, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29030712/calculating-the-consequences-of-left-shifted-nav-channel-activity-in-sick-excitable-cells
#20
Bela Joos, Benjamin M Barlow, Catherine E Morris
Two features common to diverse sick excitable cells are "leaky" Nav channels and bleb damage-damaged membranes. The bleb damage, we have argued, causes a channel kinetics based "leakiness." Recombinant (node of Ranvier type) Nav1.6 channels voltage-clamped in mechanically-blebbed cell-attached patches undergo a damage intensity dependent kinetic change. Specifically, they experience a coupled hyperpolarizing (left) shift of the activation and inactivation processes. The biophysical observations on Nav1.6 currents formed the basis of Nav-Coupled Left Shift (Nav-CLS) theory...
October 14, 2017: Handbook of Experimental Pharmacology
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