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Calcium channel subunit

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https://www.readbyqxmd.com/read/28431968/cannabinoid-cb1-and-cb2-receptors-differentially-modulate-l-and-t-type-ca-2-channels-in-rat-retinal-ganglion-cells
#1
Wen-Jing Qian, Ning Yin, Feng Gao, Yanying Miao, Qian Li, Fang Li, Xing-Huai Sun, Xiong-Li Yang, Zhongfeng Wang
Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca(2+) channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV1.2 was co-localized with T-type subunits (CaV3...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#2
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28428266/kca1-1-channels-regulate-%C3%AE-1-integrin-function-and-cell-adhesion-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#3
Mark R Tanner, Michael W Pennington, Teresina Laragione, Pércio S Gulko, Christine Beeton
Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of fibroblast-like synoviocytes isolated from the synovium of patients with rheumatoid arthritis (RA-FLS). It is a critical regulator of RA-FLS migration and invasion and therefore represents an attractive target for the therapy of RA. However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness have remained largely unknown. Here, we demonstrate that KCa1...
April 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28424266/disease-associated-extracellular-loop-mutations-in-the-adhesion-g-protein-coupled-receptor-g1-adgrg1-gpr56-differentially-regulate-downstream-signaling
#4
Ayush Kishore, Randy A Hall
Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as GPR56) underlie the neurological disorder bilateral frontoparietal polymicrogyria (BFPP). Disease-associated mutations in G1 studied to date are believed to induce complete loss of receptor function, either through disruption of receptor trafficking or signaling activity. Given that N-terminal truncation of G1 and other adhesion G protein-coupled receptors has been shown to significantly increase the receptors' constitutive signaling, we examined two different BFPP-inducing extracellular loop mutations (R565W and L640R) in the context of both full-length and N-terminally truncated (deltaNT) G1...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28413470/identification-of-genes-associated-with-the-effect-of-inflammation-on-the-neurotransmission-of-vascular-smooth-muscle-cell
#5
Shujie Gan, Shenlong Qiu, Yiwen Feng, Yanping Zhang, Qin Qian, Zhong Wan, Jingdong Tang
Vascular smooth muscle cell (VSMC) accumulation and hypertrophy are common in vascular disorders, and inflammation has a crucial role in the development of these diseases. To investigate the effect of inflammation on the neurotransmission of VSMC, bioinformatic analysis was performed, following next generation sequencing. Genes of lipopolysaccharide (LPS)-treated A7r5 cells and phosphate-buffered saline (PBS)-treated A7r5 cells were sequenced via next generation sequencing, and each assay was repeated three times...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28406893/the-chemical-basis-for-electrical-signaling
#6
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/28401650/caenorhabditis-elegans-orthologs-of-human-genes-differentially-expressed-with-age-are-enriched-for-determinants-of-longevity
#7
George L Sutphin, Grant Backer, Susan Sheehan, Shannon Bean, Caroline Corban, Teresa Liu, Marjolein J Peters, Joyce B J van Meurs, Joanne M Murabito, Andrew D Johnson, Ron Korstanje
We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in C. elegans and similar to screens that preselected candidates based on longevity-correlated metrics (e.g., stress resistance). Of the 50 genes that affected lifespan, 46 were previously unreported...
April 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/28396416/proteolytic-control-of-the-mitochondrial-calcium-uniporter-complex
#8
Chen-Wei Tsai, Yujiao Wu, Ping-Chieh Pao, Charles B Phillips, Carole Williams, Christopher Miller, Matthew Ranaghan, Ming-Feng Tsai
The mitochondrial calcium uniporter is a Ca(2+)-activated Ca(2+) channel complex mediating mitochondrial Ca(2+) uptake, a process crucial for Ca(2+) signaling, bioenergetics, and cell death. The uniporter is composed of the pore-forming MCU protein, the gatekeeping MICU1 and MICU2 subunits, and EMRE, a single-pass membrane protein that links MCU and MICU1 together. As a bridging subunit required for channel function, EMRE could paradoxically inhibit uniporter complex formation if expressed in excess. Here, we show that mitochondrial mAAA proteases AFG3L2 and SPG7 rapidly degrade unassembled EMRE using the energy of ATP hydrolysis...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28389298/stimulatory-and-inhibitory-effects-of-pkc-isozymes-are-mediated-by-serine-threonine-pkc-sites-of-the-cav2-3%C3%AE-1-subunits
#9
Senthilkumar Rajagopal, Brittney K Burton, Blanche L Fields, India O El, Ganesan L Kamatchi
Protein kinase C (PKC) isozymes modulate voltage-gated calcium (Cav) currents through Cav2.2 and Cav2.3 channels by targeting serine/threonine (Ser/Thr) phosphorylation sites of Cavα1 subunits. Stimulatory (Thr-422, Ser-2108 and Ser-2132) and inhibitory (Ser-425) sites were identified in the Cav2.2α1 subunits to PKCs βII and ε. In the current study, we investigated if the homologous sites of Cav2.3α1 subunits (stimulatory: Thr-365, Ser-1995 and Ser-2011; inhibitory: Ser-369) behaved in similar manner. Several Ala and Asp mutants were constructed in Cav2...
May 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28384108/profiling-of-circulating-serum-micrornas-in-children-with-autism-spectrum-disorder-using-stem-loop-qrt-pcr-assay
#10
Tatyana M Kichukova, Nikolay T Popov, Ivan S Ivanov, Tihomir I Vachev
BACKGROUND: Development of biomarkers for autism spectrum disorder (ASD) has still remained a challenge to date. Recently, alterations of the expression of microRNAs (miRNAs) in peripheral blood, serum and post-mortem brain tissue have been linked to ASD. miRNAs are known to be secreted by various cell types and can mediate transmission of information into recipient cells and to modulate their physiological functions. On this basis it is assumed that circulating miRNAs could be useful biomarkers for the diagnosis or prognosis of pathological conditions...
March 1, 2017: Folia Medica
https://www.readbyqxmd.com/read/28374528/calcium-activated-bkca-channels-govern-dynamic-membrane-depolarizations-of-horizontal-cells-in-rodent-retina
#11
Xiaoping Sun, Arlene A Hirano, Nicholas C Brecha, Steven Barnes
Large conductance, calcium-activated potassium (BKCa ) channels have numerous roles in neurons including the regulation of membrane excitability, intracellular [Ca(2+) ] regulation, and neurotransmitter release. In the retina, they have been identified in photoreceptors, bipolar cells, amacrine cells, and ganglion cells, but have not been conclusively identified in mammalian horizontal cells. We found that outward current recorded between -30 mV and +60 mV is carried primarily in BKCa channels in isolated horizontal cells of rats and mice...
April 4, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28373283/distinct-domains-of-the-%C3%AE-1-subunit-cytosolic-n-terminus-control-surface-expression-and-functional-properties-of-large-conductance-calcium-activated-potassium-bk-channels
#12
Lie Chen, Danlei Bi, Zen Huat Lu, Heather McClafferty, Michael J Shipston
The properties and function of large conductance calcium- and voltage- activated potassium (BK) channels are modified by the tissue specific expression of regulatory β 1-subunits. Although the short cytosolic N-terminal domain of the β 1-subunit is important for controlling both BK channel trafficking and function, whether the same, or different, regions of the N-terminus control these distinct processes remain unknown. Here we demonstrate that the first six N-terminal residues, including K3, K4 and L5, are critical for controlling functional regulation, but not trafficking, of BK channels...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28360836/genetic-tracing-of-cav3-2-t-type-calcium-channel-expression-in-the-peripheral-nervous-system
#13
Yinth A Bernal Sierra, Julia Haseleu, Alexey Kozlenkov, Valérie Bégay, Gary R Lewin
Characterizing the distinct functions of the T-type ion channel subunits Cav3.1, 3.2 or 3.3 has proven difficult due to their highly conserved amino-acid sequences and the lack of pharmacological blockers specific for each subunit. To precisely determine the expression pattern of the Cav3.2 channel in the nervous system we generated two knock-in mouse strains that express EGFP or Cre recombinase under the control of the Cav3.2 gene promoter. We show that in the brains of these animals, the Cav3.2 channel is predominantly expressed in the dentate gyrus of the hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28359200/selective-loss-of-smaller-spines-in-schizophrenia
#14
Matthew L MacDonald, Jamil Alhassan, Jason T Newman, Michelle Richard, Hong Gu, Ryan M Kelly, Alan R Sampson, Kenneth N Fish, Peter Penzes, Zachary P Wills, David A Lewis, Robert A Sweet
OBJECTIVE: Decreased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large or mature synapses. Thus, increased pruning throughout adolescence would likely result in a deficit of large spines in adulthood. Here, the authors examined the density and volume of dendritic spines in deep layer 3 of the auditory cortex of 20 schizophrenia and 20 matched comparison subjects as well as aberrant voltage-gated calcium channel subunit protein expression linked to spine loss...
March 31, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28358902/screening-for-ampa-receptor-auxiliary-subunit-specific-modulators
#15
Caleigh M Azumaya, Emily L Days, Paige N Vinson, Shaun Stauffer, Gary Sulikowski, C David Weaver, Terunaga Nakagawa
AMPA receptors (AMPAR) are ligand gated ion channels critical for synaptic transmission and plasticity. Their dysfunction is implicated in a variety of psychiatric and neurological diseases ranging from major depressive disorder to amyotrophic lateral sclerosis. Attempting to potentiate or depress AMPAR activity is an inherently difficult balancing act between effective treatments and debilitating side effects. A newly explored strategy to target subsets of AMPARs in the central nervous system is to identify compounds that affect specific AMPAR-auxiliary subunit complexes...
2017: PloS One
https://www.readbyqxmd.com/read/28351836/structural-and-biophysical-analyses-of-the-skeletal-dihydropyridine-receptor-beta-subunit-%C3%AE-1a-reveal-critical-roles-of-domain-interactions-for-stability
#16
Nicole C Norris, Soumya Joseph, Shouvik Aditya, Yamuna Karunasekara, Philip G Board, Angela F Dulhunty, Aaron J Oakley, Marco G Casarotto
Excitation-contraction (EC) coupling in skeletal muscle requires a physical interaction between the voltage-gated calcium channel dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR1) Ca2+ release channel. Although the exact molecular mechanism that initiates skeletal EC coupling is unresolved, it is clear that both the α1s and β subunits of DHPR are essential for this process. Here, we employed a series of techniques, including size-exclusion chromatography-multi-angle light scattering, differential scanning fluorimetry and isothermal calorimetry, to characterize various biophysical properties of the skeletal DHPR beta subunit β1a...
March 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28348186/biological-rationale-and-potential-clinical-use-of-gabapentin-and-pregabalin-in-bipolar-disorder-insomnia-and-anxiety-protocol-for-a-systematic-review-and-meta-analysis
#17
Kerensa T Houghton, Alexandra Forrest, Amine Awad, Lauren Z Atkinson, Sarah Stockton, Paul J Harrison, John R Geddes, Andrea Cipriani
INTRODUCTION: Gabapentin has been extensively prescribed off-label for psychiatric indications, with little established evidence of efficacy. Gabapentin and pregabalin, a very similar drug with the same mechanism of action, bind to a subunit of voltage-dependent calcium channels which are implicated in the aetiopathogenesis of bipolar disorder, anxiety and insomnia. This systematic review and meta-analysis aims to collect and critically appraise all the available evidence about the efficacy and tolerability of gabapentin and pregabalin in the treatment of bipolar disorder, insomnia and anxiety...
March 27, 2017: BMJ Open
https://www.readbyqxmd.com/read/28346321/growth-arrest-and-dna-damage-inducible-protein-45%C3%AE-mediated-dna-demethylation-of-voltage-dependent-t-type-calcium-channel-3-2-subunit-enhances-neuropathic-allodynia-after-nerve-injury-in-rats
#18
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, An-Sheng Lee, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Growth arrest and DNA-damage-inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage-inducible protein 45β-dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. METHODS: Adult male Sprague-Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage-inducible protein 45β messenger RNA-targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage-inducible protein 45β, Ro 25-6981 (an NR2B-bearing N-methyl-D-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings...
March 27, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28334599/aligning-a-synapse
#19
Daniel Kerschensteiner
Synaptic communication requires alignment of transmitter release sites with transmitter receptors. In this issue of Neuron, Wang et al. (2017) show that α2δ4 subunits link calcium channels to a trans-synaptic complex with glutamate receptors at the visual system's first synapse.
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28331181/multi-walled-carbon-nanotubes-act-as-a-chemokine-and-recruit-macrophages-by-activating-the-plc-ip3-crac-channel-signaling-pathway
#20
Hui Li, Xiao-Qiu Tan, Li Yan, Bo Zeng, Jie Meng, Hai-Yan Xu, Ji-Min Cao
The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365...
March 22, 2017: Scientific Reports
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