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Neuronal calcium channel

Jihui Seo, Jeehye Maeng, Hwa-Jung Kim
The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [³H]dopamine release in concentration- and time-dependent manners...
October 24, 2016: International Journal of Molecular Sciences
Ivan Kadurin, Laurent Ferron, Simon W Rothwell, James O Meyer, Leon R Douglas, Claudia S Bauer, Beatrice Lana, Wojciech Margas, Orpheas Alexopoulos, Manuela Nieto-Rostro, Wendy S Pratt, Annette C Dolphin
The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ...
October 26, 2016: ELife
Derek Garden, Arianna Rinaldi, Matthew F Nolan
The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex. While it is well established that climbing fibre signals are important for motor coordination, the mechanisms by which neurones in the inferior olive integrate synaptic inputs and the roles of particular ion channels are unclear. Here, we test the hypothesis that neurones in the inferior olive actively integrate glutamatergic synaptic inputs...
October 21, 2016: Journal of Physiology
Young Joon Kwon, Marni J Falk, Michael J Bennett
CLN3 disease (Spielmeyer-Vogt-Sjogren-Batten disease, previously known as classic juvenile neuronal ceroid lipofuscinosis, NCL) is a pediatric-onset progressive neurodegenerative disease characterized by progressive vision loss, seizures, loss of cognitive and motor function, and early death. While no precise biochemical mechanism or therapies are known, the pathogenesis of CLN3 disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models of CLN3 deficiency suggested that FDA-approved calcium channel antagonists may have therapeutic value...
October 20, 2016: Journal of Inherited Metabolic Disease
Donal Melanaphy, Christpher D Johnson, Maxim Kustov, Connall Watson, Lyudmyla Borysova, Theodore Burdyga, Alexander V Zholos
Transient receptor potential melastatin 8 (TRPM8) is the principal cold and menthol receptor channel. Characterized primarily for its cold sensing role in sensory neurons, it is expressed and functional in several non-neuronal tissues, including vasculature. We previously demonstrated that menthol causes vasoconstriction and vasodilatation in isolated arteries, depending on vascular tone. Here we investigated calcium's role in responses mediated by TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology and ratiometric Ca(2+) recording...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Jessica M Meves, Binhai Zheng
In this issue of Neuron, Tedeschi et al. (2016) describe the voltage-gated calcium channel subunit alpha2delta2 as a developmental switch from axon elongation to synapse formation and transmission that doubles as a suppressor of axon regeneration, providing a molecular clue for the synaptic stabilization hypothesis of CNS regeneration failure.
October 19, 2016: Neuron
Cristina Matthewman, Tyne W Miller-Fleming, David M Miller, Laura Bianchi
Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca(2+) overload. Mammalian ASIC1a and C. elegans MEC-4(d) neurotoxic channels conduct both Na(+) and Ca(2+) raising the possibility that direct Ca(2+) influx through these channels contributes to the intracellular Ca(2+) overload. However, we showed that homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca(2+) permeable yet it is neurotoxic, suggesting that Na(+) influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca(2+) block in the Xenopus oocytes expression system...
October 19, 2016: American Journal of Physiology. Cell Physiology
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
A Andrade, J Hope, A Allen, V Yorgan, D Lipscombe, J Q Pan
CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 α1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, of hCaV3.3 were identified in individuals with schizophrenia. Here we show that R1346H, but not T797M, is associated with lower hCaV3.3 protein levels, reduced glycosylation, and lower membrane surface levels of hCaV3.3 when expressed in human cell lines compared to wild-type...
October 19, 2016: Scientific Reports
Andreas Reichenbach, Andreas Bringmann
Müller glia, the principal macroglia of the retina, express diverse subtypes of adenosine and metabotropic purinergic (P2Y) receptors. Müller cells of several species, including man, also express ionotropic P2X7 receptors. ATP is liberated from Müller cells after activation of metabotropic glutamate receptors and during osmotic and mechanical induction of membrane stretch; adenosine is released through equilibrative nucleoside transporters. Müller cell-derived purines modulate the neuronal activity and have autocrine effects, for example, induction of glial calcium waves and regulation of the cellular volume...
October 2016: Journal of Ocular Pharmacology and Therapeutics
Young Youp Koh, Dong Yoon Lim
OBJECTIVE: The present study was aimed to investigate the characteristics of simvastatin, one of statins, on the catecholamine (CA) secretion from the perfused model of the isolated rat adrenal gland, and also to clarify its mechanism of action. DESIGN AND METHOD: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. RESULTS: Simvastatin inhibited ACh-evoked CA secretory response in a dose- and time-dependent fashion...
September 2016: Journal of Hypertension
Claire Guerrier, David Holcman
Binding of molecules, ions or proteins to small target sites is a generic step of cell activation. This process relies on rare stochastic events where a particle located in a large bulk has to find small and often hidden targets. We present here a hybrid discrete-continuum model that takes into account a stochastic regime governed by rare events and a continuous regime in the bulk. The rare discrete binding events are modeled by a Markov chain for the encounter of small targets by few Brownian particles, for which the arrival time is Poissonian...
October 18, 2016: Scientific Reports
D K Rieger, E Navarro, I Buendia, E Parada, L González-Lafuente, R Leon, A P Costa, I A Heinrich, K S Nascimento, B S Cavada, M G Lopez, J Egea, R B Leal
Lectins are proteins that bind cellular glycans and can modulate various neuronal functions. We have evaluated the neuroprotective effect of ConBr, a lectin purified from the seeds of Canavalia brasiliensis in a model of rat organotypic hippocampal cultures (OHCs) exposed to oxygen and glucose deprivation (OGD). OGD for 15 min followed by 24 h re-oxygenation significantly increased cell death, caused mitochondrial depolarization and increased reactive oxygen species (ROS) in CA1 region of OHCs. ConBr (0.1 μg/mL) added during the re-oxygenation period counteracted cell death, mitochondrial depolarization and overproduction of ROS induced by OGD...
October 17, 2016: Neurochemical Research
Nayeli Rivera-Ramírez, Wilber Montejo-López, María-Cristina López-Méndez, Agustín Guerrero-Hernández, Anayansi Molina-Hernández, Ubaldo García-Hernández, José-Antonio Arias-Montaño
The histamine H3 receptor (H3R) is abundantly expressed in the Central Nervous System where it regulates several functions pre and postsynaptically. H3Rs couple to Gαi/o proteins and trigger or modulate several intracellular signaling pathways, including the cAMP/PKA pathway and the opening of N- and P/Q-type voltage-gated Ca(2+) channels. In transfected cells, activation of the human H3R of 445 amino acids (hH3R445) results in phospholipase C (PLC) stimulation and release of Ca(2+) from intracellular stores...
October 12, 2016: Neurochemistry International
Meg Waraczynski, Samantha Abbott, Alex V Schultz
Previous work in our laboratory has shown that stimulating D2 dopamine receptors in the central sublenticular extended amygdala (SLEAc) can render medial forebrain bundle (MFB) stimulation less rewarding. One of the many ways in which D2 stimulation could affect the activity status of SLEAc neurons is by indirectly blocking calcium ion (Ca(2+)) influx through CaV1.3 channels. He we directly investigate the effects of blocking CaV1.3 channels on the rewarding effect of MFB stimulation. In experiment one, CaV1...
October 13, 2016: Behavioural Brain Research
Nan Zhang, Shengchang Yang, Chang Wang, Jianghua Zhang, Lifang Huo, Yiru Cheng, Chuan Wang, Zhanfeng Jia, Leiming Ren, Lin Kang, Wei Zhang
Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca(2+) homeostasis, the underlying mechanisms have not been fully explored...
October 12, 2016: Neuropharmacology
Izaskun Buendia, Giammarco Tenti, Patrycja Michalska, Iago Méndez-López, Enrique Luengo, Michele Satriani, Juan Fernando Padin Nogueira, Manuela G López, María Teresa Ramos, Antonio G García, J Carlos Menéndez, Rafael León
During brain ischemia, oxygen and glucose deprivation induces calcium overload, extensive oxidative stress, neuroinflammation and, finally, massive neuronal loss. In the search of a neuroprotective compound to mitigate this neuronal loss, we have designed and synthesized a new multitarget hybrid (ITH14001) directed at the reduction of calcium overload by acting on two regulators of calcium homeostasis; the mitochondrial Na+/Ca2+ exchanger (mNCX) and L-type voltage dependent calcium channels (VDCCs). This compound is a hybrid of CGP37157 (mNCX inhibitor) and nimodipine (L-type VDCCs blocker), and its pharmacological evaluation revealed a moderate ability to selectively inhibit both targets...
October 12, 2016: ACS Chemical Neuroscience
Anne-Marie Malfait, Richard J Miller
Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels, and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis...
October 12, 2016: Current Osteoporosis Reports
Ryan L O'Hare Doig, Carole A Bartlett, Nicole M Smith, Stuart I Hodgetts, Sarah A Dunlop, Livia Hool, Melinda Fitzgerald
Combinations of Ca(2+) channel inhibitors have been proposed as an effective means to prevent excess Ca(2+) flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca(2+) concentrations. Here, the effects of combinations of Lomerizine (Lom), YM872, memantine and/or oxATP to block voltage gated Ca(2+) channels, Ca(2+) permeable AMPA receptors, NMDA receptors and purinergic P2X7 receptors (P2X7R) respectively, on Ca(2+) concentration and viability of primary mixed cortical cultures exposed to hydrogen peroxide (H2O2) insult, were assessed...
October 7, 2016: Neuroscience
Andrea Tedeschi, Sebastian Dupraz, Claudia J Laskowski, Jia Xue, Thomas Ulas, Marc Beyer, Joachim L Schultze, Frank Bradke
Injuries to the adult CNS often result in permanent disabilities because neurons lose the ability to regenerate their axon during development. Here, whole transcriptome sequencing and bioinformatics analysis followed by gain- and loss-of-function experiments identified Cacna2d2, the gene encoding the Alpha2delta2 subunit of voltage-gated calcium channels (VGCCs), as a developmental switch that limits axon growth and regeneration. Cacna2d2 gene deletion or silencing promoted axon growth in vitro. In vivo, Alpha2delta2 pharmacological blockade through Pregabalin (PGB) administration enhanced axon regeneration in adult mice after spinal cord injury (SCI)...
September 27, 2016: Neuron
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