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Voltage Gated Calcium Channels

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https://www.readbyqxmd.com/read/28230232/carisbamate-blockade-of-t-type-voltage-gated-calcium-channels
#1
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/28220076/actions-and-mechanisms-of-polyunsaturated-fatty-acids-on-voltage-gated-ion-channels
#2
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
#3
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/28211790/flpstop-a-tool-for-conditional-gene-control-in-drosophila
#4
Yvette Erica Fisher, Helen H Yang, Jesse Isaacman-Beck, Marjorie Xie, Daryl M Gohl, Thomas R Clandinin
Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development...
February 17, 2017: ELife
https://www.readbyqxmd.com/read/28210211/app-as-a-protective-factor-in-acute-neuronal-insults
#5
REVIEW
Dimitri Hefter, Andreas Draguhn
Despite its key role in the molecular pathology of Alzheimer's disease (AD), the physiological function of amyloid precursor protein (APP) is unknown. Increasing evidence, however, points towards a neuroprotective role of this membrane protein in situations of metabolic stress. A key observation is the up-regulation of APP following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) hypoxic-ischemic conditions. While this mechanism may increase the risk or severity of AD, APP by itself or its soluble extracellular fragment APPsα can promote neuronal survival...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28202361/pre-clinical-evaluation-of-voltage-gated-calcium-channel-blockers-derived-from-the-spider-p-%C3%A2-nigriventer-in-glioma-progression
#6
Natália Fontana Nicoletti, Thaís Cristina Erig, Rafael Fernandes Zanin, Marcelo Ricardo Roxo, Nelson Pires Ferreira, Marcus Vinicius Gomez, Fernanda Bueno Morrone, Maria Martha Campos
This study investigated the effects of P/Q- and N-type voltage-gated calcium channel (VGCC) blockers derived from P. nigriventer in glioma progression, by means of in vitro and in vivo experiments. Glioma cells M059J, U-138MG and U-251MG were used to evaluate the antiproliferative effects of P/Q- and N-type VGCC inhibitors PhTx3-3 and Phα1β from P. nigriventer (0.3-100 pM), in comparison to MVIIC and MVIIA from C. magus (0.3-100 pM), respectively. The toxins were also analyzed in a glioma model induced by implantation of GL261 mouse cells...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28197074/the-first-extracellular-linker-is-important-for-several-aspects-of-the-gating-mechanism-of-human-trpa1-channel
#7
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/28195313/neuronal-sodium-channels-emerging-components-of-the-nano-machinery-of-cardiac-calcium-cycling
#8
Rengasayee Veeraraghavan, Sándor Györke, Przemysław B Radwański
Excitation-contraction coupling (ECC) is the bridge between cardiac electrical activation and mechanical contraction. It is driven by the influx of Ca(2+) across the sarcolemma triggering Ca(2+) release from the sarcoplasmic reticulum (SR) - a process termed Ca(2+) -induced Ca(2+) release (CICR) - followed by re-sequestration of Ca(2+) into the SR. The sodium calcium exchanger (NCX) inextricably couples the cycling of Ca(2+) and Na(+) in cardiac myocytes. Thus, influx of Na(+) via voltage-gated Na(+) channels (NaV ) has emerged as an important regulator of CICR both in health and in disease...
February 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28193459/epileptiform-activity-and-behavioral-arrests-in-mice-overexpressing-the-calcium-channel-subunit-%C3%AE-2%C3%AE-1
#9
Leonardo C Faria, Feng Gu, Isabel Parada, Ben Barres, Z David Luo, David A Prince
: The alpha2delta-1 subunit (α2δ-1) of voltage-gated calcium channels is a receptor for astrocyte-secreted thrombospondins that promote developmental synaptogenesis.Alpha2delta-1 receptors are upregulated in models of injury-induced peripheral pain and epileptogenic neocortical trauma associated with an enhancement of excitatory synaptic connectivity. These results lead to the hypothesis that overexpression of α2δ-1 alone in neocortex of uninjured transgenic (TG) mice might result in increased excitatory connectivity and consequent cortical hyperexcitability and epileptiform activity...
February 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28178527/an-intrinsic-transcriptional-program-underlying-synaptic-scaling-during-activity-suppression
#10
Katie Schaukowitch, Austin L Reese, Seung-Kyoon Kim, Gokhul Kilaru, Jae-Yeol Joo, Ege T Kavalali, Tae-Kyung Kim
Homeostatic scaling allows neurons to maintain stable activity patterns by globally altering their synaptic strength in response to changing activity levels. Suppression of activity by the blocking of action potentials increases synaptic strength through an upregulation of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Although this synaptic upscaling was shown to require transcription, the molecular nature of the intrinsic transcription program underlying this process and its functional significance have been unclear...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28173798/spasmogenic-and-spasmolytic-activity-of-rind-of-punica-granatum-linn
#11
Niaz Ali, Ayesha Jamil, Syed Wadood Ali Shah, Ismail Shah, Ghayour Ahmed
BACKGROUND: Rind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range. METHODS: Rind of Punica granatum was subjected to shade drying...
February 7, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28167673/ubiquitin-ligase-rnf138-promotes-episodic-ataxia-type-2-associated-aberrant-degradation-of-human-cav2-1-p-q-type-calcium-channels
#12
Ssu-Ju Fu, Chung-Jiuan Jeng, Chia-Hao Ma, Yi-Jheng Peng, Chi-Ming Lee, Ya-Ching Fang, Yi-Ching Lee, Sung-Chun Tang, Meng-Chun Hu, Chih-Yung Tang
: Voltage-gated CaV2.1 channels comprise a pore-forming α1A (CaV2.1) subunit with auxiliary α2δ and β subunits. CaV2.1 channels play an essential role in regulating synaptic signaling. Mutations in the human gene encoding CaV2.1 subunit are associated with the cerebellar disease episodic ataxia type 2 (EA2). Several EA2-causing mutants exhibit impaired protein stability and exert dominant-negative suppression of CaV2.1 wild-type (WT) protein expression via aberrant proteasomal degradation...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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/28161890/homology-guided-mutational-analysis-reveals-the-functional-requirements-for-antinociceptive-specificity-of-crmp2-derived-peptides
#14
Aubin Moutal, Wennan Li, Yue Wang, Weina Ju, Shizhen Luo, Song Cai, Liberty François-Moutal, Samantha Perez-Miller, Jackie Hu, Erik T Dustrude, Todd W Vanderah, Vijay Gokhale, May Khanna, Rajesh Khanna
BACKGROUND AND PURPOSE: N-type voltage-gated calcium (CaV2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Despite CaV2.2 antagonism being recommended as first-line treatment for neuropathic pain, calcium-current blocking gabapentinoids inadequately alleviate chronic pain symptoms and are often mired by numerous side-effects. Collapsin response mediator protein 2 (CRMP2) targets CaV2.2 to the sensory neuron membrane, and allosterically modulates Cav2...
February 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28150887/differential-effects-of-energy-deprivation-on-intracellular-sodium-homeostasis-in-neurons-and-astrocytes
#15
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/28150151/structure-based-assessment-of-disease-related-mutations-in-human-voltage-gated-sodium-channels
#16
REVIEW
Weiyun Huang, Minhao Liu, S Frank Yan, Nieng Yan
Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Nav channels, with Nav1.1 and Nav1.5 each harboring more than 400 mutations. Nav channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Nav channels are required to understand their function and disease mechanisms...
February 1, 2017: Protein & Cell
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/28127114/cacna1b-cav2-2-overexpression-and-its-association-with-clinicopathologic-characteristics-and-unfavorable-prognosis-in-non-small-cell-lung-cancer
#18
Xiaoyu Zhou, Wei Wang, Shu Zhang, Xudong Wang, Zhiyuan Tang, Jun Gu, Jun Li, Jianan Huang
CACNA1B (Cav2.2) encodes an N-type voltage-gated calcium channel (VGCC) ubiquitously expressed in brain and peripheral nervous system that is important for regulating neuropathic pain. Because intracellular calcium concentration is a key player in cell proliferation and apoptosis, VGCCs are implicated in tumorigenesis. Recent studies have identified CACNA1B (Cav2.2) being overexpressed in prostate and breast cancer tissues when compared to adjacent normal tissues; however, its role in non-small cell lung cancer (NSCLC) has not been investigated...
2017: Disease Markers
https://www.readbyqxmd.com/read/28115397/loss-of-%C3%AE-2%C3%AE-1-calcium-channel-subunit-function-increases-the-susceptibility-for-diabetes
#19
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
https://www.readbyqxmd.com/read/28114421/immediate-effects-of-repetitive-magnetic-stimulation-on-single-cortical-pyramidal-neurons
#20
Jineta Banerjee, Mary E Sorrell, Pablo A Celnik, Galit Pelled
Repetitive Transcranial Magnetic Stimulation (rTMS) has been successfully used as a non-invasive therapeutic intervention for several neurological disorders in the clinic as well as an investigative tool for basic neuroscience. rTMS has been shown to induce long-term changes in neuronal circuits in vivo. Such long-term effects of rTMS have been investigated using behavioral, imaging, electrophysiological, and molecular approaches, but there is limited understanding of the immediate effects of TMS on neurons...
2017: PloS One
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