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https://www.readbyqxmd.com/read/29773754/a-critical-neurodevelopmental-role-for-l-type-voltage-gated-calcium-channels-in-neurite-extension-and-radial-migration
#1
Satoshi Kamijo, Yuichiro Ishii, Shin-Ichiro Horigane, Kanzo Suzuki, Masamichi Ohkura, Junichi Nakai, Hajime Fujii, Sayaka Takemoto-Kimura, Haruhiko Bito
In spite of many association studies linking gene polymorphisms and mutations of L-type Voltage-Gated Ca2+ Channels (VGCC) in neurodevelopmental disorders, such as autism and schizophrenia, specific L-type VGCC roles during brain development remain unclear. Yet, calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring and fine tuning of growing networks. To bridge this gap, we performed submembraneous calcium imaging using a membrane-tethered genetically-encoded calcium indicator (GECI) Lck-G-CaMP7...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29755321/voltage-gated-calcium-channel-activation-by-backpropagating-action-potentials-downregulates-nmdar-function
#2
Anne-Kathrin Theis, Balázs Rózsa, Gergely Katona, Dietmar Schmitz, Friedrich W Johenning
The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs) propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs). For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs) result in long-term enhancement of spine VGCCs...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29738885/regulation-of-seizure-induced-mecp2-ser421-phosphorylation-in-the-developing-brain
#3
Evan C Rosenberg, Jocelyn J Lippman-Bell, Marcus Handy, Samantha S Soldan, Sanjay Rakhade, Cristina Hilario-Gomez, Kaitlyn Folweiler, Leah Jacobs, Frances E Jensen
Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of CaV 1.2 L-type voltage gated calcium (Ca2+ ) channels (LT-VGCCs) and Ca2+ -permeable AMPARs (CP-AMPARs) lacking GluA2 subunits. We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca2+ -dependent signaling pathways including that of methyl-CPG-binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome...
May 5, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29729231/calcium-influx-differentially-regulates-migration-velocity-and-directedness-in-response-to-electric-field-application
#4
R Babona-Pilipos, N Liu, A Pritchard-Oh, A Mok, D Badawi, M R Popovic, C M Morshead
Neural precursor cells (NPCs) respond to externally applied direct current electrical fields (DCEFs) by undergoing rapid and directed migration toward the cathode in a process known as galvanotaxis. It is unknown if the underlying mechanisms of galvanotactic migration is common to non-electrosensitive cells and if so, how NPCs and other galvanotactic cells sense and transduce electrical fields into cellular motility. In this study, we show that distinct aspects of NPC galvanotactic migration: motility (quantified through |velocity|) and directedness, are differentially regulated by calcium...
May 2, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29692966/conjoint-glutamic-acid-decarboxylase-65-and-p-q-voltage-gated-calcium-channel-antibodies-in-autoimmune-epilepsy-a-case-report
#5
Mohamed AlKhaja, Ammar AlKawi, Mahmoud Abu-Ata, Asma Mohammaddin
Numerous autoantibodies are implicated in the pathogenesis of autoimmune epilepsy. In the past decade, many case series reported the association of glutamic acid decarboxylase 65 (GAD 65) antibodies with epilepsy. Conjoint presence of GAD 65 antibodies with antinuclear, anti-thyroid, and anti-parietal cell antibodies has often been demonstrated. However, concomitant elevated levels of GAD 65 and P/Q voltage gated calcium channel (VGCC) antibodies is rare. We report a case of autoimmune epilepsy with conjoint GAD 65 and P/Q VGCC antibodies in the absence of malignancy...
2018: Epilepsy & Behavior Case Reports
https://www.readbyqxmd.com/read/29667130/beneficial-effects-of-the-calcium-channel-blocker-ctk-01512-2-in-a-mouse-model-of-multiple-sclerosis
#6
Rodrigo B M Silva, Samuel Greggio, Gianina T Venturin, Jaderson C da Costa, Marcus V Gomez, Maria M Campos
Voltage-gated calcium channels (VGCCs) play a critical role in neuroinflammatory diseases, such as multiple sclerosis (MS). CTK 01512-2 is a recombinant version of the peptide Phα1β derived from the spider Phoneutria nigriventer, which inhibits N-type VGCC/TRPA1-mediated calcium influx. We investigated the effects of this molecule in the mouse model of experimental autoimmune encephalomyelitis (EAE). The effects of CTK 01512-2 were compared to those displayed by ziconotide-a selective N-type VGCC blocker clinically used for chronic pain-and fingolimod-a drug employed for MS treatment...
April 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29656989/substituent-effect-of-n-benzylated-gramine-derivatives-that-prevent-the-pp2a-inhibition-and-dissipate-the-neuronal-ca-2-overload-as-a-multitarget-strategy-for-the-treatment-of-alzheimer-s-disease
#7
Dorleta Gonzalez, Raquel L Arribas, Lucia Viejo, Rocio Lajarin-Cuesta, Cristobal de Los Rios
Following the premises of the multitarget-directed ligands approach for the drug R&D against neurodegenerative diseases, where Alzheimer's disease (AD) outstands, we have synthesized and evaluated analogues of the gramine derivative ITH12657 (1-benzyl-5-methyl-3-(piperidin-1-ylmethyl-1H-indole, 2), which had shown important neuroprotective properties, such as blocking effect of voltage-gated Ca2+ channels (VGCC), and prevention of phosphoprotein phosphatase 2A (PP2A) inhibition. The new analogues present different substitutions at the pending phenyl ring, what slightly modified their pharmacological characteristics...
April 9, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29603093/oxaliplatin-modulates-the-characteristics-of-voltage-gated-calcium-channels-and-action-potentials-in-small-dorsal-root-ganglion-neurons-of-rats
#8
Linda-Isabell Schmitt, Markus Leo, Christoph Kleinschnitz, Tim Hagenacker
Oxaliplatin is important for treating colorectal cancer. Although oxaliplatin is highly effective, it has severe side effects, of which neurotoxicity in dorsal root ganglion (DRG) neurons is one of the most common. The key mechanisms of this neurotoxicity are still controversial. However, disturbances of calcium homeostasis in DRG neurons have been suggested to mediate oxaliplatin neurotoxicity. By using whole-cell patch-clamp and current-clamp techniques, as well as immunocytochemical staining, we examined the influence of short- and long-term exposure to oxaliplatin on voltage-gated calcium channels (VGCC) and different VGCC subtypes in small DRG neurons of rats in vitro...
March 30, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29573716/wi-fi-is-an-important-threat-to-human-health
#9
Martin L Pall
Repeated Wi-Fi studies show that Wi-Fi causes oxidative stress, sperm/testicular damage, neuropsychiatric effects including EEG changes, apoptosis, cellular DNA damage, endocrine changes, and calcium overload. Each of these effects are also caused by exposures to other microwave frequency EMFs, with each such effect being documented in from 10 to 16 reviews. Therefore, each of these seven EMF effects are established effects of Wi-Fi and of other microwave frequency EMFs. Each of these seven is also produced by downstream effects of the main action of such EMFs, voltage-gated calcium channel (VGCC) activation...
March 21, 2018: Environmental Research
https://www.readbyqxmd.com/read/29572644/expression-of-a-constitutively-active-human-insulin-receptor-in-hippocampal-neurons-does-not-alter-vgcc-currents
#10
H N Frazier, K L Anderson, S Maimaiti, A O Ghoweri, S D Kraner, G J Popa, K K Hampton, M D Mendenhall, C M Norris, R J Craven, O Thibault
Memory and cognitive decline are the product of numerous physiological changes within the aging brain. Multiple theories have focused on the oxidative, calcium, cholinergic, vascular, and inflammation hypotheses of brain aging, with recent evidence suggesting that reductions in insulin signaling may also contribute. Specifically, a reduction in insulin receptor density and mRNA levels has been implicated, however, overcoming these changes remains a challenge. While increasing insulin receptor occupation has been successful in offsetting cognitive decline, alternative molecular approaches should be considered as they could bypass the need for brain insulin delivery...
March 23, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29563180/variations-in-ca-2-influx-can-alter-ca-2-chelator-based-estimates-of-ca-2-channel-synaptic-vesicle-coupling-distance
#11
Yukihiro Nakamura, Maria Reva, David A DiGregorio
The timing and probability of synaptic vesicle fusion from presynaptic terminals is governed by the strength of coupling between voltage-gated Ca2+ channels (VGCCs) and Ca2+ sensors for exocytosis. This VGCC-sensor coupling distance can be estimated from the fractional block of vesicular release by exogenous Ca2+ chelators. However, estimates of this distance can depend on many biophysical factors, whose contributions have not been thoroughly explored. Using numerical simulations of Ca2+ reaction and diffusion, as well as vesicular release, we examined the contributions of conductance, density, and open duration of VGCCs, as well as the influence of endogenous Ca2+ buffers on the inhibition of exocytosis by EGTA...
March 21, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29556214/calcium-channels-in-postnatal-development-of-rat-pancreatic-beta-cells-and-their-role-in-insulin-secretion
#12
Neivys García-Delgado, Myrian Velasco, Carmen Sánchez-Soto, Carlos Manlio Díaz-García, Marcia Hiriart
Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29510211/the-disease-modifying-drug-candidate-sak3-improves-cognitive-impairment-and-inhibits-amyloid-beta-deposition-in-app-knock-in-mice
#13
Hisanao Izumi, Yasuharu Shinoda, Takashi Saito, Takaomi C Saido, Keita Sato, Yasushi Yabuki, Yotaro Matsumoto, Yoshitomi Kanemitsu, Yoshihisa Tomioka, Nona Abolhassani, Yusaku Nakabeppu, Kohji Fukunaga
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of elderly dementia in the world. At present, acetylcholine inhibitors, such as donepezil, galantamine and rivastigmine, are used for AD therapy, but the therapeutic efficacy is limited. We recently proposed T-type voltage-gated Ca2+ channels' (T-VGCCs) enhancer as a new therapeutic candidate for AD. In the current study, we confirmed the pharmacokinetics of SAK3 in the plasma and brain of mice using ultra performance liquid chromatography-tandem mass spectrometry...
May 1, 2018: Neuroscience
https://www.readbyqxmd.com/read/29492218/cav3-1-overexpression-is-associated-with-negative-characteristics-and-prognosis-in-non-small-cell-lung-cancer
#14
Aleksi Suo, Allison Childers, Adrijana D'Silva, Lars F Petersen, Shannon Otsuka, Michelle Dean, Haocheng Li, Emeka K Enwere, Brant Pohorelic, Alexander Klimowicz, Ivana A Souza, Jawed Hamid, Gerald W Zamponi, DGwyn Bebb
Introduction: Voltage-gated calcium channels (VGCC) have been found to be differentially expressed in several different tumor types, but their role in tumor growth, malignant invasion, metastases and impact on clinical outcomes has not been clarified. Materials and Methods: From a cohort database of 193 patients with early-stage NSCLC, 163 formalin-fixed paraffin-embedded specimens were available for analysis to construct tissue microarrays. Cav3.1 protein expression was detected using fluorescence immunohistochemistry, and quantified using automated image acquisition and analysis...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29473171/nimodipine-confers-clinical-improvement-in-two-models-of-experimental-autoimmune-encephalomyelitis
#15
Jens Ingwersen, Lorenzo De Santi, Britta Wingerath, Jonas Graf, Barbara Koop, Reiner Schneider, Christina Hecker, Friederike Schröter, Mary Bayer, Anna Dorothee Engelke, Michael Dietrich, Philipp Albrecht, Hans-Peter Hartung, Pasquale Annunziata, Orhan Aktas, Tim Prozorovski
Multiple sclerosis (MS) is characterized by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca2+ overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca2+ influx by pharmacological modulation of Ca2+ channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy...
February 23, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29414872/suramin-induced-neurotoxicity-preclinical-models-and-neuroprotective-strategies
#16
David von der Ahe, Petra Huehnchen, Mustafa Balkaya, Sarah Peruzzaro, Matthias Endres, Wolfgang Boehmerle
Suramin is a trypan blue analogon originally developed to treat protozoan infections, which was found to have diverse antitumor effects. One of the most severe side effects in clinical trials was the development of a peripheral sensory-motor polyneuropathy. In this study, we aimed to investigate suramin-induced neuropathy with a focus on calcium (Ca2+ ) homeostasis as a potential pathomechanism. Adult C57Bl/6 mice treated with a single injection of 250 mg/kg bodyweight suramin developed locomotor and sensory deficits, which were confirmed by electrophysiological measurements showing a predominantly sensory axonal-demyelinating polyneuropathy...
February 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29374372/targeting-the-cacna1a-ires-as-a-treatment-for-spinocerebellar-ataxia-type-6
#17
Parviz Daniel Hejazi Pastor, Xiaofei Du, Sarah Fazal, Andre N Davies, Christopher M Gomez
We have discovered that the P/Q-type voltage-gated Ca2+ channel (VGCC) gene, CACNA1A, encodes both the α1A (Cav2.1) subunit and a newly recognized transcription factor, α1ACT, by means of a novel internal ribosomal entry site (IRES) within the α1A C-terminal coding region. α1ACT, when mutated with an expansion of the polyglutamine tract in the C-terminus, gives rise to spinocerebellar ataxia type 6 (SCA6). Because silencing of the entire CACNA1A gene would result in the loss of the essential Cav2.1 channel, the IRES controlling α1ACT expression is an excellent target for selective silencing of α1ACT as a therapeutic intervention for SCA6...
February 2018: Cerebellum
https://www.readbyqxmd.com/read/29371604/swell1-is-a-glucose-sensor-regulating-%C3%AE-cell-excitability-and-systemic-glycaemia
#18
Chen Kang, Litao Xie, Susheel K Gunasekar, Anil Mishra, Yanhui Zhang, Saachi Pai, Yiwen Gao, Ashutosh Kumar, Andrew W Norris, Samuel B Stephens, Rajan Sah
Insulin secretion is initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+ -mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (ICl,SWELL ) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated ICl,SWELL and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling...
January 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29246857/new-cav2-calcium-channel-gating-modifiers-with-agonist-activity-and-therapeutic-potential-to-treat-neuromuscular-disease
#19
Man Wu, Hayley V White, Blake A Boehm, Christopher J Meriney, Kaylan Kerrigan, Michael Frasso, Mary Liang, Erika M Gotway, Madeleine R Wilcox, Jon W Johnson, Peter Wipf, Stephen D Meriney
Voltage-gated calcium channels (VGCCs) are critical regulators of many cellular functions, including the activity-dependent release of chemical neurotransmitter from nerve terminals. At nerve terminals, the Cav2 family of VGCCs are closely positioned with neurotransmitter-containing synaptic vesicles. The relationship between calcium ions and transmitter release is such that even subtle changes in calcium flux through VGCCs have a strong influence on the magnitude of transmitter released. Therefore, modulators of the calcium influx at nerve terminals have the potential to strongly affect transmitter release at synapses...
March 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29237755/differential-contribution-of-ca-2-sources-to-day-and-night-bk-current-activation-in-the-circadian-clock
#20
Joshua P Whitt, Beth A McNally, Andrea L Meredith
Large conductance K+ (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca2+ (Ca2+ i ). To enable this regulation, BK channels functionally couple to both voltage-gated Ca2+ channels (VGCCs) and channels mediating Ca2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca2+ i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca2+ i are reduced...
February 5, 2018: Journal of General Physiology
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