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Voltage-dependent calcium channels

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https://www.readbyqxmd.com/read/28230278/deletion-of-psychiatric-risk-gene-cacna1c-impairs-hippocampal-neurogenesis-in-cell-autonomous-fashion
#1
Bianca Völkening, Kai Schönig, Golo Kronenberg, Dusan Bartsch, Tillmann Weber
Ca(2+) is a universal signal transducer which fulfills essential functions in cell development and differentiation. CACNA1C, the gene encoding the alpha-1C subunit (i.e., Cav 1.2) of the voltage-dependent l-type calcium channel (LTCC), has been implicated as a risk gene in a variety of neuropsychiatric disorders. To parse the role of Cav 1.2 channels located on astrocyte-like stem cells and their descendants in the development of new granule neurons, we created Tg(GLAST-CreERT2) /Cacna1c(fl/fl) /RCE:loxP mice, a transgenic tool that allows cell-type-specific inducible deletion of Cacna1c...
February 23, 2017: Glia
https://www.readbyqxmd.com/read/28230232/carisbamate-blockade-of-t-type-voltage-gated-calcium-channels
#2
Do Young Kim, Fang-Xiong Zhang, Stan T Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G Sullivan, S R Wayne Chen, Gerald W Zamponi, Jong M Rho
OBJECTIVES: Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca(2+) ]i . METHODS: We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload-Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca(2+) ]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T-type voltage-gated Ca(2+) channels...
February 23, 2017: Epilepsia
https://www.readbyqxmd.com/read/28227903/development-of-a-detailed-model-of-calcium-dynamics-at-the-postsynaptic-spine-of-an-excitatory-synapse
#3
Eric Y Hu, Jean-Marie C Bouteiller, Dong Song, Theodore W Berger, Eric Y Hu, Jean-Marie C Bouteiller, Dong Song, Theodore W Berger, Jean-Marie C Bouteiller, Eric Y Hu, Dong Song, Theodore W Berger
Postsynaptic calcium dynamics play a critical role in synaptic plasticity, but are often difficult to measure in experimental protocols due to their relatively fast rise and decay times, and the small spine dimensions. To circumvent these limitations, we propose to develop a computational model of calcium dynamics in the postsynaptic spine. This model integrates the main elements that participate in calcium concentration influx, efflux, diffusion and buffering. These consist of (i) spine geometry; (ii) calcium influx through NMDA receptors and voltage-dependent calcium channels (VDCC); (iii) calcium efflux with plasma membrane calcium pumps (PMCA) and sodium-calcium exchangers (NCX); (iv) intracellular calcium stores; and (v) calcium buffers...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28220076/actions-and-mechanisms-of-polyunsaturated-fatty-acids-on-voltage-gated-ion-channels
#4
REVIEW
Fredrik Elinder, Sara I Liin
Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28214378/calcium-signaling-through-l-type-calcium-channels-role-in-pathophysiology-of-spinal-nociceptive-transmission
#5
REVIEW
Olivier Roca-Lapirot, Houda Radwani, Franck Aby, Frédéric Nagy, Marc Landry Pascal Fossat
L-type voltage-gated calcium channels (VGCCs) are ubiquitous channels in the central nervous system. L-type calcium channels (LTCs) are mostly post-synaptic channels regulating neuronal firing and gene expression. They play a role in important physio-pathological processes such as learning and memory, Parkinson's disease, autism and, as recognized more recently, in the pathophysiology of pain processes. Classically, the fundamental role of these channels in cardiovascular functions has limited the use of classical molecules to treat LTC-dependent disorders...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28209036/-primary-culture-and-functional-identification-of-distal-pulmonary-artery-smooth-muscle-cells-in-mice
#6
M C Li, Y Q Chen, C T Zhang, Q Jiang, W J Lu, J Wang
Objective: To establish a method of isolation and primary culture of mice distal pulmonary artery smooth muscle cells (PASMCs) and identify the functional properties. Methods: PASMCs were harvested from the distal pulmonary artery (PA) tissue of mice by enzymatic digestion of collagenaseⅠand papain; and the growth characteristics were observed under inverted microscope and identified by Immunofluorescence technique. Effects on the intracellular calcium ion concentration of distal PASMCs were detected by Fura-2-AM fluorescent probe tracer under a fluorescence microscope in Krebs solution containing clopiazonic acid (CPA) and nifedipin (Nif)...
February 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28199072/genetic-risk-score-analysis-in-early-onset-bipolar-disorder
#7
Paul E Croarkin, Joan L Luby, Kelly Cercy, Jennifer R Geske, Marin Veldic, Matthew Simonson, Paramjit T Joshi, Karen Dineen Wagner, John T Walkup, Malik M Nassan, Alfredo B Cuellar-Barboza, Leah Casuto, Susan L McElroy, Peter S Jensen, Mark A Frye, Joanna M Biernacka
OBJECTIVE: In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). METHODS: Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria...
February 14, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28197715/vacuolar-ion-channels-in-the-liverwort-marchantia-polymorpha-influence-of-ion-channel-inhibitors
#8
Mateusz Koselski, Kazimierz Trebacz, Halina Dziubinska
Potassium-permeable slow activating vacuolar channels (SV) and chloride-permeable channels in the vacuole of the liverwort Marchantia polymorpha were characterized in respect to calcium dependence, selectivity, and pharmacology. The patch-clamp method was used in the study of ion channel activity in the vacuoles from the liverwort Marchantia polymorpha. The whole-vacuole recordings allowed simultaneous observation of two types of currents-predominant slow activated currents recorded at positive voltages and fast activated currents recorded at negative voltages...
February 14, 2017: Planta
https://www.readbyqxmd.com/read/28197074/the-first-extracellular-linker-is-important-for-several-aspects-of-the-gating-mechanism-of-human-trpa1-channel
#9
Lenka Marsakova, Ivan Barvik, Vlastimil Zima, Lucie Zimova, Viktorie Vlachova
Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel involved in pain, inflammation and itching. This channel gates in response to many irritant and proalgesic agents, and can be modulated by calcium and depolarizing voltage. While the closed-state structure of TRPA1 has been recently resolved, also having its open state is essential for understanding how this channel works. Here we use molecular dynamics simulations combined with electrophysiological measurements and systematic mutagenesis to predict and explore the conformational changes coupled to the expansion of the presumptive channel's lower gate...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28179473/dynamic-regulation-of-homer-binding-to-group-i-mglurs-by-preso1-and-converging-kinase-cascades
#10
Jia-Hua Hu, Paul F Worley, Paul Kammermeier
In rat sympathetic neurons from the superior cervical ganglia (SCG) expressing metabotropic glutamate receptors (mGluRs) 1 or 5, overexpression of scaffolding Homer proteins, which bind to a Homer ligand in their C-termini, cause receptor clustering and uncoupling from ion channel modulation. In the absence of recombinant Homer protein overexpression, uncoupling of mGluRs from voltage dependent channels can be induced by expression of Preso1, an adaptor of proline directed kinases that phosphorylates the Homer ligand and recruits binding of endogenous Homer proteins...
February 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28176276/maintained-ltp-and-memory-are-lost-by-zn-2-influx-into-dentate-granule-cells-but-not-ca-2-influx
#11
Atsushi Takeda, Haruna Tamano, Marie Hisatsune, Taku Murakami, Hiroyuki Nakada, Hiroaki Fujii
The idea that maintained LTP and memory are lost by either increase in intracellular Zn(2+) in dentate granule cells or increase in intracellular Ca(2+) was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K(+) into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K(+)-induced increase in intracellular Zn(2+) but not high K(+)-induced increase in intracellular Ca(2+). High K(+)-induced disturbances of LTP and intracellular Zn(2+) are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels...
February 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28168949/erg-28-controls-bk-channel-trafficking-in-the-er-to-regulate-synaptic-function-and-alcohol-response-in-c-elegans
#12
Kelly H Oh, James J Haney, Xiaohong Wang, Chiou-Fen Chuang, Janet E Richmond, Hongkyun Kim
Voltage- and calcium-dependent BK channels regulate calcium-dependent cellular events such as neurotransmitter release by limiting calcium influx. Their plasma membrane abundance is an important factor in determining BK current and thus regulation of calcium-dependent events. In C. elegans, we show that ERG-28, an endoplasmic reticulum (ER) membrane protein, promotes the trafficking of SLO-1 BK channels from the ER to the plasma membrane by shielding them from premature degradation. In the absence of ERG-28, SLO-1 channels undergo aspartic protease DDI-1-dependent degradation, resulting in markedly reduced expression at presynaptic terminals...
February 7, 2017: ELife
https://www.readbyqxmd.com/read/28165324/inhibitory-peptidergic-modulation-of-c-elegans-serotonin-neurons-is-gated-by-t-type-calcium-channels
#13
Kara E Zang, Elver Ho, Niels Ringstad
Serotonin is an evolutionarily ancient molecule that functions in generating and modulating many behavioral states. Although much is known about how serotonin acts on its cellular targets, how serotonin release is regulated in vivo remains poorly understood. In the nematode C. elegans, serotonin neurons that drive female reproductive behavior are directly modulated by inhibitory neuropeptides. Here, we report the isolation of mutants in which inhibitory neuropeptides fail to properly modulate serotonin neurons and the behavior they mediate...
February 6, 2017: ELife
https://www.readbyqxmd.com/read/28165042/relationship-between-auxiliary-gamma-subunits-and-mallotoxin-on-bk-channel-modulation
#14
Xin Guan, Qin Li, Jiusheng Yan
The large-conductance, calcium- and voltage-activated K(+)(BK) channel consists of the pore-forming α subunits (BKα) and auxiliary subunits. The auxiliary γ1-3 subunits potently modulate the BK channel by shifting its voltage-dependence of channel activation toward the hyperpolarizing direction by approximately 145 mV (γ1), 100 mV (γ2), and 50 mV (γ3). Mallotoxin is a potent small-molecule BK channel activator. We analyzed the relationship between mallotoxin and the γ subunits in their BK channel-activating effects in membrane patches excised from HEK-293 cells...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159537/diethyl-4-4-dihydroxy-8-3-neolign-7-7-dien-9-9-dionate-exhibits-antihypertensive-activity-in-rats-through-increase-in-intracellular-cgmp-level-and-blockade-of-calcium-channels
#15
Arjun Singh, B Sathish Kumar, Sarfaraz Alam, Hina Iqbal, Mohammad Shafiq, Feroz Khan, Arvind S Negi, Kashif Hanif, Debabrata Chanda
We report here the antihypertensive and vasorelaxant potential of some steroidal and non-steroidal compounds identified through a library of compounds. All the novel analogues showed vasorelaxant potential in isolated rat aorta. The most potent lead neolignan1 (Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate) produced concentration dependent relaxation with [pD2 5.16 ± 0.05; n=16 and Emax 96.97% ± 1.12%; n=16]. The neolignan1 relaxation is independent of endothelium and is sensitive to ODQ (1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one; a blocker of soluble guanylyl cyclase (sGC) which synthesizes cGMP (cyclic guanosine monophosphate))...
January 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28150887/differential-effects-of-energy-deprivation-on-intracellular-sodium-homeostasis-in-neurons-and-astrocytes
#16
REVIEW
Niklas J Gerkau, Cordula Rakers, Gabor C Petzold, Christine R Rose
The maintenance of a low intracellular sodium concentration by the Na(+) /K(+) -ATPase (NKA) is critical for brain function. In both neurons and glial cells, NKA activity is required to counteract changes in the sodium gradient due to opening of voltage- and ligand-gated channels and/or activation of sodium-dependent secondary active transporters. Because NKA consumes about 50% of cellular ATP, sodium homeostasis is strictly dependent on an intact cellular energy metabolism. Despite the high energetic costs of electrical signaling, neurons do not contain significant energy stores themselves, but rely on a close metabolic interaction with surrounding astrocytes...
February 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28137877/camkii-modulates-sodium-current-in-neurons-from-epileptic-scn2a-mutant-mice
#17
Christopher H Thompson, Nicole A Hawkins, Jennifer A Kearney, Alfred L George
Monogenic epilepsies with wide-ranging clinical severity have been associated with mutations in voltage-gated sodium channel genes. In the Scn2a(Q54) mouse model of epilepsy, a focal epilepsy phenotype is caused by transgenic expression of an engineered NaV1.2 mutation displaying enhanced persistent sodium current. Seizure frequency and other phenotypic features in Scn2a(Q54) mice depend on genetic background. We investigated the neurophysiological and molecular correlates of strain-dependent epilepsy severity in this model...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28137618/astrocyte-neuron-interaction-in-diphenyl-ditelluride-toxicity-directed-to-the-cytoskeleton
#18
Luana Heimfarth, Fernanda da Silva Ferreira, Paula Pierozan, Moara Rodrigues Mingori, José Cláudio Fonseca Moreira, João Batista Teixeira da Rocha, Regina Pessoa-Pureur
Diphenylditelluride (PhTe)2 is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe)2 caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-d-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28116717/measuring-t-type-calcium-channel-currents-in-isolated-vascular-smooth-muscle-cells
#19
Ivana Y Kuo, Caryl E Hill
Patch clamp electrophysiology is a powerful tool that has been important in isolating and characterizing the ion channels that govern cellular excitability under physiological and pathophysiological conditions. The ability to enzymatically dissociate blood vessels and acutely isolate vascular smooth muscle cells has enabled the application of patch clamp electrophysiology to the identification of diverse voltage dependent ion channels that ultimately control vasoconstriction and vasodilation. Since intraluminal pressure results in depolarization of vascular smooth muscle, the channels that control the voltage dependent influx of extracellular calcium are of particular interest...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28115397/loss-of-%C3%AE-2%C3%AE-1-calcium-channel-subunit-function-increases-the-susceptibility-for-diabetes
#20
Vincenzo Mastrolia, Sylvia M Flucher, Gerald J Obermair, Mathias Drach, Helene Hofer, Erik Renström, Arnold Schwartz, Jörg Striessnig, Bernhard E Flucher, Petronel Tuluc
Reduced pancreatic β-cell function or mass is the critical problem in developing diabetes. Insulin release from β-cells depends on Ca(2+) influx through high voltage-gated Ca(2+) channels (HVCC). Ca(2+) influx also regulate insulin synthesis, insulin granule priming and contribute to β-cell electrical activity. The HVCC are multi-subunit protein complexes composed of a pore-forming α1 and auxiliary β and α2δ subunits. α2δ is a key regulator of membrane incorporation and function of HVCCs. Here we show that genetic deletion of α2δ-1, the dominant α2δ subunit in pancreatic islets, results in glucose intolerance and diabetes without affecting insulin sensitivity...
January 23, 2017: Diabetes
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