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N-type calcium channels

R J Wang, M L Wen, Q Zhou, X W Wei, H Li, Y B Zhao, Y F Qi, J Luan, X F Zhou
Objective: To elucidate the association between large conductance calcium-activated potassium channels (BKCa ) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BKCa inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0...
March 24, 2018: Zhonghua Xin Xue Guan Bing za Zhi
Cecilia Castillo, Juan Carlos Martinez, Marines Longart, Lisbeth García, Marianela Hernández, Jeismar Carballo, Héctor Rojas, Lorena Matteo, Liliana Casique, José Leonardo Escalona, Yuryanni Rodríguez, Jessica Rodriguez, Deyanell Hernández, Domingo Balbi, Raimundo Villegas
Collapsin Response Mediator Protein 2 (CRMP2) is an intracellular protein involved in axon and dendrite growth and specification. In this study, CRMP2 was identified in a conditioned media derived from degenerated sciatic nerves (CM). On cultured rat hippocampal neurons, acute extracellular application of CM or partially purified recombinant CRMP2 produced an increase in cytoplasmic calcium. The increase in cytoplasmic calcium was mostly mediated through NMDA receptors, with a minor contribution of N-type VDCC, and it was maintained as long as CM was present...
April 15, 2018: Neuroscience
Gladstone C McDowell, Joseph Winchell
OBJECTIVES: The majority of patients seeking medical care for chronic pain consult a primary care physician (PCP). Because systemic opioids are commonly prescribed to patients with chronic pain, PCPs are attempting to balance the competing priorities of providing adequate pain relief while reducing risks for opioid misuse and overdose. It is important for PCPs to be aware of pain management strategies other than systemic opioid dose escalation when patients with chronic pain fail to respond to conservative therapies and to initiate a multimodal treatment plan...
March 15, 2018: Postgraduate Medicine
Alessandra Romanelli, Alessandra Affinito, Concetta Avitabile, Silvia Catuogno, Paola Ceriotti, Margherita Iaboni, Jessica Modica, Geroloma Condorelli, Daniele Catalucci
Small therapeutic peptides represent a promising field for the treatment of pathologies such as cardiac diseases. However, the lack of proper target-selective carriers hampers their translation towards a potential clinical application. Aptamers are cell-specific carriers that bind with high affinity to their specific target. However, some limitations on their conjugation to small peptides and the functionality of the resulting aptamer-peptide chimera exist. Here, we generated a novel aptamer-peptide chimera through conjugation of the PDGFRβ-targeting Gint4...
2018: PloS One
Feng Yi, Linda G Zachariassen, Katherine N Dorsett, Kasper B Hansen
NMDA-type glutamate receptors mediate excitatory synaptic transmission in the central nervous system and play critical roles in many neuronal processes. The physiological roles of NMDA receptors are shaped by their functional properties, which are highly dependent on subunit composition. Most NMDA receptors are assembled from two GluN1 and two GluN2 subunits, but diversity in subunit composition is made possible by eight GluN1 splice variants (i.e. isoforms) and four distinct GluN2 subunits (GluN2A-D). We demonstrate using FRET-FLIM that GluN1-1a and GluN1-1b isoforms, which includes or lacks residues encoded by exon 5, form triheteromeric GluN1-1a/GluN1-1b/GluN2A (1a/1b/2A) and GluN1-1a/GluN1-1b/GluN2B (1a/1b/2B) receptors...
February 26, 2018: Molecular Pharmacology
Lilian R Ferreira Faro, Miguel Alfonso, Vania Moraes Ferreira, Rafael Durán
The possible role of voltage-sensitive calcium channels (VSCC) activation on the HgCl2 -induced dopamine release was investigated using selective VSCC blockers and the dopamine levels were measured by HPLC from samples obtained by in vivo brain microdialysis. Infusion of HgCl2 in nicardipine (10 or 100 μM) or flunaricine (10 μM) pretreated animals had no significant effect on dopamine release induced by HgCl2 . Pretreatment with 100 μM flunaricine, 20 μM ω-conotoxin MVIIC, or ω-conotoxin GVIA significantly decreased the HgCl2 -induced dopamine release over 61%, 88%, and 99%, respectively...
February 12, 2018: Environmental Toxicology and Pharmacology
P J M van Kleeff, J Gao, S Mol, N Zwart, H Zhang, K W Li, A H de Boer
Potassium (K+ ) is a vital ion for many processes in the plant and fine-tuned ion channels control the K+ -fluxes across the plasma membrane. GORK is an outward-rectifying K+ -channel with important functions in stomatal closure and in root K+ -homeostasis. In this study, post-translational modification of the Arabidopsis GORK ion channel and its regulation by 14-3-3 proteins was investigated. To investigate the possible interaction between GORK and 14-3-3s an in vivo pull-down from an Arabidopsis protein extract with recombinant GORK C-terminus (GORK-C) indeed identified endogenous 14-3-3s (LAMBDA, CHI, NU) as binding partners in a phosphorylation dependent manner...
February 16, 2018: Plant Physiology and Biochemistry: PPB
Teerawat Wiwatpanit, Natalie N Remis, Aisha Ahmad, Yingjie Zhou, John C Clancy, Mary Ann Cheatham, Jaime García-Añoveros
Acquired hearing loss is the predominant neurodegenerative condition associated with aging in humans. Although mutations on several genes are known to cause congenital deafness in newborns, few genes have been implicated in age-related hearing loss (ARHL), perhaps because its cause is likely polygenic. Here, we generated mice lacking lysosomal calcium channel mucolipins 3 and 1 and discovered that both male and female mice suffered a polygenic form of hearing loss. While mucolipin 1 is ubiquitously expressed in all cells, mucolipin 3 is expressed in a small subset of cochlear cells -hair cells (HCs) and marginal cells of the stria vascularis- and very few other cell types...
February 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Satoko Nozato, Koichi Yamamoto, Yoichi Nozato, Masao Takeda, Kazuhiro Hongyo, Miyuki Takeya, Hiroshi Akasaka, Yoichi Takami, Yasushi Takeya, Ken Sugimoto, Norihisa Ito, Hiromi Rakugi
Recent studies suggest that L-type calcium channel blockers (CCBs) contribute to reducing blood pressure (BP) variability. We investigated whether inhibition of the N-type calcium channel has an additional effect on BP variability by comparing the effect of L-type and L/N-type CCBs on home BP variability in elderly hypertensive patients. Twenty-six hypertensive patients (≥65 years) were subjected to repeated changes with the administration of amlodipine (L-type CCB) and cilnidipine (L/N-type CCB) every 2 months...
February 15, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Yan Yang, Yihui Cui, Kangning Sang, Yiyan Dong, Zheyi Ni, Shuangshuang Ma, Hailan Hu
The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine...
February 14, 2018: Nature
Jessica Morand, Claire Arnaud, Jean-Louis Pepin, Diane Godin-Ribuot
We investigated the effects of intermittent hypoxia (IH), such as that encountered in severe obstructive sleep apnea (OSA) patients, on the development and severity of myocardial ischemia-related ventricular arrhythmias. Rats were exposed to 14 days of IH (30 s at 5%O 2 and 30 s at 21%O 2 , 8 h·day -1 ) or normoxia (N, similar air-air cycles) and submitted to a 30-min coronary ligature. Arterial blood pressure (BP) and ECG were recorded for power spectral analysis, ECG interval measurement and arrhythmia quantification...
February 14, 2018: Scientific Reports
Sébastien J Dumas, Gilles Bru-Mercier, Audrey Courboulin, Marceau Quatredeniers, Catherine Rücker-Martin, Fabrice Antigny, Morad K Nakhleh, Benoit Ranchoux, Elodie Gouadon, Maria-Candida Vinhas, Matthieu Vocelle, Nicolas Raymond, Peter Dorfmüller, Elie Fadel, Frédéric Perros, Marc Humbert, Sylvia Cohen-Kaminsky
Background -Excessive proliferation and apoptosis resistance in pulmonary vascular cells underlie vascular remodeling in pulmonary arterial hypertension (PAH). Specific treatments for PAH exist, mostly targeting endothelial dysfunction, but high pulmonary arterial pressure still causes heart failure and death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of vascular cells to increase glutaminolysis and glutamate production. The N-methyl-D-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also expressed on vascular cells, but its role in PAH is unknown...
February 14, 2018: Circulation
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
February 7, 2018: Cellular Physiology and Biochemistry
Jie Zhou, Mengbin Qin, Huilin Wang, Jiaping He, Hongzong Fu, Huirong Shi, Zhihai Liang, Guodu Tang
Ghrelin influences pancreatic endocrine and exocrine functions, regulates intracellular calcium [Ca2+]i levels, and has an anti-inflammatory role in acute pancreatitis. This study investigated the role of endogenous ghrelin in the expression of Cav 1.2 (L-type of Ca2+ channel) and Cav 2.2 (N-type of Ca2+ channel) in acute pancreatitis. For this purpose, acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) rat models were established. Cav 1.2 and Cav 2.2 expression was assessed by immunohistochemistry in the pancreatic tissues of rats; ghrelin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serum levels were detected using ELISA...
February 13, 2018: International Journal of Molecular Medicine
Klaus Schaffler, Weizhong He, Paul Passier, Katherine Tracy, Allam Fakhoury, Jeffrey Paul
Objective: Evaluate the analgesic/antihyperalgesic effects of ASP9226, a state-dependent N-type voltage-gated calcium channel inhibitor, in healthy male subjects. Design: Randomized, double-blind, double-dummy, placebo- and active comparator-controlled crossover study. Setting: HPR Dr. Schaffler GmbH, Munich, Germany. Subject: Healthy male subjects aged 18-55 years. Methods: Twenty-four eligible subjects were randomly assigned to one of four treatment sequences and received single doses of ASP9226 (30 mg or 50 mg), pregabalin (150 mg), or placebo during four treatment periods...
January 25, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Joy M Johnson, Johannes Thürich, Elena Kristin Petutschnig, Lothar Altschmied, Doreen Meichsner, Irena Sherameti, Julian Dindas, Anna Mrozinska, Christian Paetz, Sandra S Scholz, Alexandra Cu Furch, Volker Lipka, Rainer Hedrich, Bernd Schneider, Aleš Svatoš, Ralf Oelmüller
Piriformospora indica, an endophytic root-colonizing fungus, efficiently promotes plant growth and induces resistance to abiotic stress and biotic diseases. The fungal cell wall extract induces cytoplasmic calcium [Ca2+]cyt elevation in host plant roots. Here, we show that an elici-tor-active cell wall moiety, released by P. indica into the medium, is cellotriose (CT). CT in-duces a mild defense-like response including the production of reactive oxygen species, changes in membrane potentials and the expression of genes involved in growth regulation and root development...
January 25, 2018: Plant Physiology
Jamileth More, Barbara Bruna, Pedro Lobos, José Luis Galaz, Paula Figueroa, Silvia Namias, Gina Sanchez, Genaro Barrientos, José Luis Valdes, Andrea C Paula-Lima, Cecilia Hidalgo, Tatiana Adasme
Previous studies indicate that hippocampal synaptic plasticity and spatial memory processes entail calcium release from intracellular stores mediated by ryanodine receptor (RyR) channels. In particular, RyR-mediated Ca2+ release is central for the dendritic spine remodeling induced by Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin that stimulates complex signaling pathways leading to memory-associated protein synthesis and structural plasticity. AIMS: To examine if up-regulation of type-2 RyR (RyR2) channels and the spine remodeling induced by BDNF entail reactive oxygen species (ROS) generation, and to test if RyR2 down-regulation affects BDNF-induced spine remodeling and spatial memory...
January 22, 2018: Antioxidants & Redox Signaling
Zhuguo Liu, Peter Bartels, Mahsa Sadeghi, Tianpeng Du, Qing Dai, Cui Zhu, Shuo Yu, Shuo Wang, Mingxin Dong, Ting Sun, Jiabin Guo, Shuangqing Peng, Ling Jiang, David J Adams, Qiuyun Dai
We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells...
January 17, 2018: Scientific Reports
Juan A Estrada, Marc P Kaufman
Mu opioid G-protein coupled receptors (MOR) interact with ion channels to decrease neuronal excitability. In humans, intrathecal administration of the MOR agonist, fentanyl, inhibits the exercise pressor reflex, an effect that can be attributed to either the opening of inward rectifying potassium channels (GIRK) or the closing of N-type calcium channels. The purpose of this study was to determine if the highly selective MOR agonist DAMGO attenuates the exercise pressor reflex, and which of these two channels are responsible for this effect...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Jonghyun Choi, Yongwoo Jang, Haedong Kim, Jungwon Wee, Sinyoung Cho, Woo Sung Son, Sung Min Kim, Young Duk Yang
Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2+ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2+ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to Ca2+ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both Ca2+ and noxious heat...
January 16, 2018: BMB Reports
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