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Voltage-gated calcium channels

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https://www.readbyqxmd.com/read/28343066/calcium-triggers-reversal-of-calmodulin-on-nested-anti-parallel-sites-in-the-iq-motif-of-the-neuronal-voltage-dependent-sodium-channel-nav1-2
#1
Liam Hovey, C Andrew Fowler, Ryan Mahling, Zesen Lin, Mark Stephen Miller, Dagan C Marx, Jesse B Yoder, Elaine H Kim, Kristin M Tefft, Brett C Waite, Michael D Feldkamp, Liping Yu, Madeline A Shea
Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel NaV1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca(2+))4-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca(2+))4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1...
March 9, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28338073/veratridine-produces-distinct-calcium-response-profiles-in-mouse-dorsal-root-ganglia-neurons
#2
Zainab A Mohammed, Ciara Doran, David Grundy, Mohammed A Nassar
Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an "agonist" in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336549/eavk-segment-c-sequence-confers-ca-2-dependent-changes-to-the-kinetics-of-full-length-human-ano1
#3
Peter R Strege, Simon J Gibbons, Amelia Mazzone, Cheryl E Bernard, Arthur Beyder, Gianrico Farrugia
Anoctamin1 (Ano1, TMEM16A) is a calcium-activated chloride channel specifically expressed in interstitial cells of Cajal (ICC) of the gastrointestinal (GI) tract muscularis propria. Ano1 is necessary for normal electrical slow waves and ICC proliferation. The full length human Ano1 sequence includes an additional exon, exon "0," at the N-terminus. Ano1 with exon "0" (Ano1(0)) had a lower EC50 for intracellular calcium ([Ca(2+)]i) and faster chloride current (ICl) kinetics. The Ano1 alternative splice variant with segment "c" encoding exon 13 expresses on the first intracellular loop four additional amino acid residues, EAVK, which alter ICl at low [Ca(2+)]i Exon 13 is expressed in 75-100% of Ano1 transcripts in most human tissues but only 25% in human stomach...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28330839/evolutionary-insights-into-t-type-ca-2-channel-structure-function-and-ion-selectivity-from-the-trichoplax-adhaerens-homologue
#4
Carolyn L Smith, Salsabil Abdallah, Yuen Yan Wong, Phuong Le, Alicia N Harracksingh, Liana Artinian, Arianna N Tamvacakis, Vincent Rehder, Thomas S Reese, Adriano Senatore
Four-domain voltage-gated Ca(2+) (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells...
March 22, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28326013/molecular-chaperone-calnexin-regulates-the-function-of-drosophila-sodium-channel-paralytic
#5
Xi Xiao, Changyan Chen, Tian-Ming Yu, Jiayao Ou, Menglong Rui, Yuanfen Zhai, Yijing He, Lei Xue, Margaret S Ho
Neuronal activity mediated by voltage-gated channels provides the basis for higher-order behavioral tasks that orchestrate life. Chaperone-mediated regulation, one of the major means to control protein quality and function, is an essential route for controlling channel activity. Here we present evidence that Drosophila ER chaperone Calnexin colocalizes and interacts with the α subunit of sodium channel Paralytic. Co-immunoprecipitation analysis indicates that Calnexin interacts with Paralytic protein variants that contain glycosylation sites Asn313, 325, 343, 1463, and 1482...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28322832/dapoxetine-induces-neuroprotective-effects-against-glutamate-induced-neuronal-cell-death-by-inhibiting-calcium-signaling-and-mitochondrial-depolarization-in-cultured-rat-hippocampal-neurons
#6
Imju Jeong, Ji Seon Yang, Yi Jae Hong, Hee Jung Kim, Sang June Hahn, Shin Hee Yoon
Selective serotonin reuptake inhibitors (SSRIs) have an inhibitory effect on various ion channels including Ca(2+) channels. We used fluorescent dye-based digital imaging, whole-cell patch clamping and cytotoxicity assays to examine whether dapoxetine, a novel rapid-acting SSRI, affect glutamate-induced calcium signaling, mitochondrial depolarization and neuronal cell death in cultured rat hippocampal neurons. Pretreatment with dapoxetine for 10min inhibited glutamate-induced intracellular free Ca(2+) concentration ([Ca(2+)]i) increases in a concentration-dependent manner (Half maximal inhibitory concentration= 4...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28318089/a-cacna1d-mutation-in-a-patient-with-persistent-hyperinsulinaemic-hypoglycaemia-heart-defects-and-severe-hypotonia
#7
S E Flanagan, F Vairo, M B Johnson, R Caswell, T W Laver, H Lango Allen, K Hussain, S Ellard
Congenital hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or it may present as part of a wider syndrome. For approximately 40%-50% of individuals with this condition, sequence analysis of the known HH genes identifies a causative mutation. Identifying the underlying genetic aetiology in the remaining cases is important as a genetic diagnosis will inform on recurrence risk, may guide medical management and will provide valuable insights into β-cell physiology. We sequenced the exome of a child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay as well as the unaffected parents...
March 20, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28315127/inherited-ventricular-arrhythmias-the-role-of-the-multi-subunit-structure-of-the-l-type-calcium-channel-complex
#8
Julie Briot, Marie-Philippe Tétreault, Benoîte Bourdin, Lucie Parent
The normal heartbeat is conditioned by transient increases in the intracellular free Ca(2+) concentration. Ca(2+) influx in cardiomyocytes is regulated by the activity of the heteromeric L-type voltage-activated CaV1.2 channel. A complex network of interactions between the different proteins forming the ion channel supports the kinetics and the activation gating of the Ca(2+) influx. Alterations in the biophysical and biochemical properties or in the biogenesis in any of these proteins can lead to serious disturbances in the cardiac rhythm...
March 18, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315020/novel-biomarkers-for-non-functioning-invasive-pituitary-adenomas-were-identified-by-using-analysis-of-micrornas-expression-profile
#9
Silin Wu, Ye Gu, Yuying Huang, Tyh-Chai Wong, Hailin Ding, Tengfei Liu, Yu Zhang, Xiaobiao Zhang
The microRNAs (miRNAs) are involved in multiple pathological processes among various types of tumors. However, the functions of miRNAs in benign brain tumors are largely unexplored. In order to explore the pathogenesis of the invasiveness in non-functional pituitary adenoma (NFPA), the miRNAs expression profile was analyzed between invasive and non-invasive non-functional pituitary adenoma by miRNAs microarray. Six most significant differentially expressed miRNAs were identified including four upregulated miRNAs hsa-miR-181b-5p, hsa-miR-181d, hsa-miR-191-3p, and hsa-miR-598 and two downregulated miRNAs hsa-miR-3676-5p and hsa-miR-383...
March 17, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/28303257/neurod2-regulates-stim1-expression-and-store-operated-calcium-entry-in-cortical-neurons
#10
Gokhan Guner, Gizem Guzelsoy, Fatma Sadife Isleyen, Gulcan Semra Sahin, Cansu Akkaya, Efil Bayam, Eser Ilgin Kotan, Alkan Kabakcioglu, Gulayse Ince-Dunn
Calcium signaling controls many key processes in neurons, including gene expression, axon guidance, and synaptic plasticity. In contrast to calcium influx through voltage- or neurotransmitter-gated channels, regulatory pathways that control store-operated calcium entry (SOCE) in neurons are poorly understood. Here, we report a transcriptional control of Stim1 (stromal interaction molecule 1) gene, which is a major sensor of endoplasmic reticulum (ER) calcium levels and a regulator of SOCE. By using a genome-wide chromatin immunoprecipitation and sequencing approach in mice, we find that NEUROD2, a neurogenic transcription factor, binds to an intronic element within the Stim1 gene...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28297674/nanoscale-structural-plasticity-of-the-active-zone-matrix-modulates-presynaptic-function
#11
Oleg O Glebov, Rachel E Jackson, Christian M Winterflood, Dylan M Owen, Ellen A Barker, Patrick Doherty, Helge Ewers, Juan Burrone
The active zone (AZ) matrix of presynaptic terminals coordinates the recruitment of voltage-gated calcium channels (VGCCs) and synaptic vesicles to orchestrate neurotransmitter release. However, the spatial organization of the AZ and how it controls vesicle fusion remain poorly understood. Here, we employ super-resolution microscopy and ratiometric imaging to visualize the AZ structure on the nanoscale, revealing segregation between the AZ matrix, VGCCs, and putative release sites. Long-term blockade of neuronal activity leads to reversible AZ matrix unclustering and presynaptic actin depolymerization, allowing for enrichment of AZ machinery...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28296171/calcium-dependent-nedd4-2-upregulation-mediates-degradation-of-the-cardiac-sodium-channel-nav1-5-implications-for-heart-failure
#12
Ling Luo, Feifei Ning, Yuan Du, Bingxue Song, Dandan Yang, Samantha C Salvage, Ya Wang, James A Fraser, Shetuan Zhang, Aiqun Ma, Tingzhong Wang
AIM: Reductions of voltage-gated sodium channel (Nav1.5) function/expression provide a slowed-conduction substrate for cardiac arrhythmias. Nedd4-2, which is activated by calcium, post-translationally modulates Nav1.5. We aim to investigate whether elevated intracellular calcium ([Ca(2+) ]i ) reduces Nav1.5 through Nedd4-2 and its role in heart failure (HF). METHODS: Using a combination of biochemical, electrophysiological, cellular and in vivo methods, we tested the effect and mechanism of calcium on Nedd4-2 and in turn Nav1...
March 10, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28280418/intracellular-calcium-dependent-regulation-of-the-sperm-specific-calcium-activated-potassium-channel-hslo3-by-the-bkca-activator-ldd175
#13
Tharaka Darshana Wijerathne, Jihyun Kim, Dongki Yang, Kyu Pil Lee
Plasma membrane hyperpolarization associated with activation of Ca(2+)-activated K(+) channels plays an important role in sperm capacitation during fertilization. Although Slo3 (slowpoke homologue 3), together with the auxiliary γ2-subunit, LRRC52 (leucine-rich-repeat-containing 52), is known to mediate the pH-sensitive, sperm-specific K(+) current KSper in mice, the molecular identity of this channel in human sperm remains controversial. In this study, we tested the classical BKCa activators, NS1619 and LDD175, on human Slo3, heterologously expressed in HEK293 cells together with its functional interacting γ2 subunit, hLRRC52...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28278376/stapled-voltage-gated-calcium-channel-cav-%C3%AE-interaction-domain-aid-peptides-act-as-selective-protein-protein-interaction-inhibitors-of-cav-function
#14
Felix Findeisen, Marta Campiglio, Hyunil Jo, Fayal Abderemane-Ali, Christine H Rumpf, Lianne Pope, Nathan D Rossen, Bernhard E Flucher, William F DeGrado, Daniel L Minor
For many voltage-gated ion channels (VGICs) creation of a properly functioning ion channel requires the formation of specific protein protein interactions between the transmembrane pore-forming subunits and cytoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta xylyl (m xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (CaV) pore forming subunit α interaction domain (AID) and cytoplasmic β subunit (CaVβ)...
March 9, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28274920/h2o2-augments-cytosolic-calcium-in-nucleus-tractus-solitarii-neurons-via-multiple-voltage-gated-calcium-channels
#15
Tim D Ostrowski, Heather A Dantzler, Luis Polo-Parada, David D Kline
Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H2O2) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown...
March 8, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28274876/hypotonic-stress-promotes-atp-release-reactive-oxygen-species-production-and-cell-proliferation-via-trpv4-activation-in-rheumatoid-arthritis-rat-synovial-fibroblasts
#16
Fen Hu, Zhenhai Hui, Wei Wei, Jianyu Yang, Ziyuan Chen, Bu Guo, Fulin Xing, Xinzheng Zhang, Leiting Pan, Jingjun Xu
Rheumatoid arthritis (RA) is a chronic and systemic autoimmune-disease with complex and unclear etiology. Hypotonicity of synovial fluid is a typical characteristic of RA, which may play pivotal roles in RA pathogenesis. In this work, we studied the responses of RA synovial fibroblasts to hypotonic stress in vitro and further explored the underlying mechanisms. Data showed that hyposmotic solutions significantly triggered increases in cytosolic calcium concentration ([Ca(2+)]c) of synoviocytes. Subsequently, it caused rapid release of ATP, as well as remarkable production of intracellular reactive oxygen species (ROS)...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28267430/mapping-the-function-of-neuronal-ion-channels-in-model-and-experiment
#17
William F Podlaski, Alexander Seeholzer, Lukas N Groschner, Gero Miesenböck, Rajnish Ranjan, Tim P Vogels
Ion channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretation of simulations. However, the number of published models, and the lack of standardization, make the comparison of ion channel models with one another and with experimental data difficult. Here, we present a framework for the automated large-scale classification of ion channel models. Using annotated metadata and responses to a set of voltage-clamp protocols, we assigned 2378 models of voltage- and calcium-gated ion channels coded in NEURON to 211 clusters...
March 6, 2017: ELife
https://www.readbyqxmd.com/read/28264432/electrophysiological-characterization-of-the-antarease-metalloprotease-from-tityus-serrulatus-venom
#18
Irene Zornetta, Michele Scorzeto, Pablo Victor Mendes Dos Reis, Maria E De Lima, Cesare Montecucco, Aram Megighian, Ornella Rossetto
Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction...
February 27, 2017: Toxins
https://www.readbyqxmd.com/read/28264196/molecular-basis-of-ancestral-vertebrate-electroreception
#19
Nicholas W Bellono, Duncan B Leitch, David Julius
Elasmobranch fishes, including sharks, rays, and skates, use specialized electrosensory organs called ampullae of Lorenzini to detect extremely small changes in environmental electric fields. Electrosensory cells within these ampullae can discriminate and respond to minute changes in environmental voltage gradients through an unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and the big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate (Leucoraja erinacea) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important for the detection of specific, weak electrical signals...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28262416/the-auxiliary-calcium-channel-subunit-%C3%AE-2%C3%AE-4-is-required-for-axonal-elaboration-synaptic-transmission-and-wiring-of-rod-photoreceptors
#20
Yuchen Wang, Katherine E Fehlhaber, Ignacio Sarria, Yan Cao, Norianne T Ingram, Debbie Guerrero-Given, Ben Throesch, Kristin Baldwin, Naomi Kamasawa, Toshihisa Ohtsuka, Alapakkam P Sampath, Kirill A Martemyanov
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca(2+) channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV1...
March 22, 2017: Neuron
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