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https://www.readbyqxmd.com/read/28522805/nitric-oxide-donor-protects-against-acetic-acid-induced-gastric-ulcer-in-rats-via-s-nitrosylation-of-trpv1-on-vagus-nerve
#1
Ting Han, Yan Tang, Jing Li, Bing Xue, Liping Gong, Jingxin Li, Xiao Yu, Chuanyong Liu
This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy. SNP increased the jejunal mesenteric afferent discharge in a dose-depended manner, which was largely diminished by pretreatment of S-nitrosylation blocker N-ethylmaleimide, TRPV1 antagonist capsazepine, genetic deletion of TRPV1, or vagotomy...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28520841/chronic-inflammatory-pain-impairs-mglur5-mediated-depolarization-induced-suppression-of-excitation-in-the-anterior-cingulate-cortex
#2
Baolin Guo, Jiaqi Wang, Han Yao, Keke Ren, Jing Chen, Jing Yang, Guohong Cai, Haiying Liu, Yunlong Fan, Wenting Wang, Shengxi Wu
The anterior cingulate cortex (ACC) is a critical hub for nociceptive perception and pain-related anxiety. Long-term synaptic plasticity in ACC was found to be important for chronic inflammatory pain and pain-related anxiety. As short-term synaptic plasticity, depolarization-induced suppression of excitation (DSE) is involved in several conditions, such as chronic stress, epilepsy, and autism. However, it is still unknown whether DSE in the ACC is involved in the central sensitization of pain and anxiety. Using a whole-cell patch clamp, calcium imaging, western blot, and behavioral testing, we found that DSE was induced by a 2 s depolarization in postsynaptic pyramidal cells in ACC...
May 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28515683/a-population-of-projection-neurons-that-inhibits-the-lateral-horn-but-excites-the-antennal-lobe-through-chemical-synapses-in-drosophila
#3
Kazumichi Shimizu, Mark Stopfer
In the insect olfactory system, odor information is transferred from the antennal lobe (AL) to higher brain areas by projection neurons (PNs) in multiple AL tracts (ALTs). In several species, one of the ALTs, the mediolateral ALT (mlALT), contains some GABAergic PNs; in the Drosophila brain, the great majority of ventral PNs (vPNs) are GABAergic and project through this tract to the lateral horn (LH). Most excitatory PNs (ePNs), project through the medial ALT (mALT) to the mushroom body (MB) and the LH. Recent studies have shown that GABAergic vPNs play inhibitory roles at their axon terminals in the LH...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28514017/isopimaric-acid-a-multi-targeting-ion-channel-modulator-reducing-excitability-and-arrhythmicity-in-a-spontaneously-beating-mouse-atrial-cell-line
#4
Sajjad Salari, Malin Silverå Ejneby, Johan Brask, Fredrik Elinder
AIM: Atrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. METHODS: Spontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. RESULTS: 1-25 μmol L(-1) IPA reduced the action potential frequency by up to 50%...
May 17, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28513236/enhanced-gap-junctional-channel-activity-between-vascular-smooth-muscle-cells-in-cerebral-artery-of-spontaneously-hypertensive-rats
#5
Li-Jie Wang, Ke-Tao Ma, Wen-Yan Shi, Ying-Zi Wang, Lei Zhao, Xin-Yan Chen, Xin-Zhi Li, Xue-Wei Jiang, Zhong-Shuang Zhang, Li Li, Jun-Qiang Si
The aim of the present study is to investigate the effects of hypertension on the gap junctions between vascular smooth muscle cells (VSMCs) in the cerebral arteries (CAs) of spontaneously hypertensive rats (SHRs). The functions of gap junctions in the CAs of VSMCs in SHRs and control normotensive Wistar-Kyoto (WKY) rats were studied using whole-cell patch clamp recordings and pressure myography, and the expression levels of connexins were analyzed using reverse transcription-quantitative polymerase chain reaction and Western blot analyses...
May 17, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28512142/a-well-known-potassium-channel-plays-a-critical-role-in-lysosomes
#6
Michael X Zhu
Whole-endolysosome patch clamping presents new opportunities to identify and characterize channels pivotal for these acidic organelles. In this issue (Wang et al., 2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612123), the identification of a role for the large conductance calcium-activated potassium channel brings new thinking about regulation of lysosome membrane potential and function.
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28511915/altered-ionic-currents-and-amelioration-by-igf-1-and-pacap-in-motoneuron-derived-cells-modelling-sbma
#7
Aura M Jiménez Garduño, Leon J Juárez-Hernández, María J Polanco, Laura Tosatto, Daniela Michelatti, Daniele Arosio, Manuela Basso, Maria Pennuto, Carlo Musio
Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a motor neuron disease caused by the expansion of a polymorphic CAG tandem repeat encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is triggered by the binding of mutant AR to its natural ligands, testosterone and dihydrotestosterone (DHT). To investigate the neuronal alterations of motor neuron cell models of SBMA, we applied patch-clamp methods to verify how polyQ expansions in the AR alter cell ionic currents...
May 10, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28511870/atp-sensitive-k-channels-maintain-resting-membrane-potential-in-interstitial-cells-of-cajal-from-the-mouse-colon
#8
Ji Sun Na, Chansik Hong, Man Woo Kim, Chan Guk Park, Hyun Goo Kang, Mei Jin Wu, Han Yi Jiao, Seok Choi, Jae Yeoul Jun
To investigate the role of ATP-sensitive K(+) (KATP) channels on pacemaker activity in interstitial cells of Cajal (ICC), whole-cell patch clamping, RT-PCR, and intracellular Ca(2+) ([Ca(2+)]i) imaging were performed in cultured colonic ICC. Pinacidil (a K(+) channel opener) hyperpolarized the membrane and inhibited the generation of pacemaker potential, and this effect was reversed by glibenclamide (a KATP channel blocker). RT-PCR showed that Kir 6.1 and SUR2B were expressed in Ano-1 positive colonic ICC. Glibenclamide depolarized the membrane and increased pacemaker potential frequency...
May 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28508747/voltage-gated-na-currents-in-human-dorsal-root-ganglion-neurons
#9
Xiulin Zhang, Birgit T Priest, Inna Belfer, Michael S Gold
Available evidence indicates voltage-gated Na(+) channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons...
May 16, 2017: ELife
https://www.readbyqxmd.com/read/28507079/distance-constraints-on-activation-of-trpv4-channels-by-akap150-bound-pkc%C3%AE-in-arterial-myocytes
#10
Sendoa Tajada, Claudia M Moreno, Samantha O'Dwyer, Sean Woods, Daisuke Sato, Manuel F Navedo, L Fernando Santana
TRPV4 (transient receptor potential vanilloid 4) channels are Ca(2+)-permeable channels that play a key role in regulating vascular tone. In arterial myocytes, opening of TRPV4 channels creates local increases in Ca(2+) influx, detectable optically as "TRPV4 sparklets." TRPV4 sparklet activity can be enhanced by the action of the vasoconstrictor angiotensin II (AngII). This modulation depends on the activation of subcellular signaling domains that comprise protein kinase C α (PKCα) bound to the anchoring protein AKAP150...
May 15, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28506844/proarrhythmic-risk-assessment-using-conventional-and-new-in-vitro-assays
#11
Sonia Goineau, Vincent Castagné
Drug-induced QT prolongation is a major safety issue in the drug discovery process. This study was conducted to assess the electrophysiological responses of four substances using established preclinical assays usually used in regulatory studies (hERG channel or Purkinje fiber action potential) and a new assay (human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)-field potential). After acute exposure, moxifloxacin and dofetilide concentration-dependently decreased IKr amplitude (IC50 values: 102 μM and 40 nM, respectively) and lengthened action potential (100 μM moxifloxacin: +23% and 10 nM dofetilide: +18%) and field potential (300 μM moxifloxacin: +76% and 10 nM dofetilide: +38%) durations...
May 12, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28504338/plasmonic-based-electrochemical-impedance-imaging-of-electrical-activities-in-single-cells
#12
Xian-Wei Liu, Yunze Yang, Wei Wang, Shaopeng Wang, Ming Gao, Jie Wu, Nongjian Tao
Studying electrical activities in cells, such as action potential and its propagation in neurons, requires a sensitive and non-invasive analytical tool that can image local electrical signals with high spatial and temporal resolutions. Here we report a plasmonic-based electrochemical impedance imaging technique to study transient electrical activities in single cells. The technique is based on the conversion of the electrical signal into a plasmonic signal, which is imaged optically without labels. We demonstrate imaging of the fast initiation and propagation of action potential within single neurons, and validate the imaging technique with the traditional patch clamp technique...
May 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28500173/tgf-%C3%AE-1-transforming-growth-factor-%C3%AE-1-plays-a-pivotal-role-in-cardiac-myofibroblast-arrhythmogenicity
#13
Nicolò Salvarani, Ange Maguy, Stefano A De Simone, Michele Miragoli, Florian Jousset, Stephan Rohr
BACKGROUND: TGF-β1 (transforming growth factor-β1) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β1 alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro. METHODS AND RESULTS: Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β1, applied for 24 to 48 hours at clinically relevant concentrations (≤2...
May 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28499969/corticotropin-releasing-hormone-modulates-airway-vagal-preganglionic-neurons-of-sprague-dawley-rats-at-multiple-synaptic-sites-via-activation-of-its-type-1-receptors-implications-for-stress-associated-airway-vagal-excitation
#14
Yuhong Guo, Xianxia Yan, Xingxin Chen, Ding He, Ming Zeng, Yonghua Chen, Chunmei Xia, Dongying Qiu, Jijiang Wang
Corticotropin-releasing hormone release is the final common pathway of stress-associated neuroendocrine responses. This study tested how corticotropin-releasing hormone modulates airway vagal preganglionic neurons. Airway vagal preganglionic neurons in neonatal rats were retrogradely labeled with fluorescent dye and identified in medullary slices, and their responses to corticotropin-releasing hormone (200nmolL(-1)) were examined using whole-cell patch clamp. The results show that under current clamp, corticotropin-releasing hormone (200nmolL(-1)) depolarized airway vagal preganglionic neurons and significantly increased the rate of their spontaneous firing...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28499095/trpm7-is-involved-in-volume-regulation-in-salivary-glands
#15
J M Kim, S Choi, K Park
Under hypotonic conditions, the regulatory volume decrease (RVD) is essential to maintain physiological homeostasis and functions in diverse biological systems. Intracellular Ca(2+) has been reported as an important mediator of this response, but the underlying Ca(2+) mechanism responsible for RVD is still controversial. Here we investigate the role of Ca(2+) in the RVD response using live-cell imaging, microspectrofluorimetry, and a patch-clamp technique. A typical RVD was observed in submandibular gland acinar cells after swelling in a hypotonic solution, whereas intracellular Ca(2+) chelation completely inhibited the RVD response...
May 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28498410/neuropeptide-y-suppresses-epileptiform-discharges-by-regulating-ampa-receptor-glur2-subunit-in-rat-hippocampal-neurons
#16
Wei Bu, Wen-Qing Zhao, Wen-Ling Li, Chang-Zheng Dong, Zhe Zhang, Qi-Jun Li
The present study aimed to investigate the effects of neuropeptide Y (NPY) on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor glutamate receptor 2 (GluR2) subunit in epileptiform discharge hippocampal neurons. Hippocampal neurons were harvested from neonatal Sprague‑Dawley rats aged <24 h and primarily cultured in vitro. At day 12 following culture, hippocampal neurons were divided into the following groups: Control, Mg2+‑free, NPY+Mg2+‑free and BIBP3226+NPY+Mg2+‑free...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28496108/alpha7-nicotinic-acetylcholine-receptor-agonist-promotes-retinal-ganglion-cell-function-via-modulating-gabaergic-presynaptic-activity-in-a-chronic-glaucomatous-model
#17
Xujiao Zhou, Yun Cheng, Rong Zhang, Gang Li, Boqi Yang, Shenghai Zhang, Jihong Wu
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28495885/proteolytic-cleavage-of-the-hydrophobic-domain-in-the-cav%C3%AE-2%C3%AE-1-subunit-improves-assembly-and-activity-of-cardiac-cav1-2-channels
#18
Emilie Segura, Benoîte Bourdin, Marie-Philippe Tétreault, Julie Briot, Bruce G Allen, Gaétan Mayer, Lucie Parent
Voltage-gated L-type CaV1.2 channels in cardiomyocytes exist as heteromeric complexes with the pore-forming CaVα1, CaVβ, and CaVα2δ1 subunits. The full complement of subunits is required to reconstitute the native-like properties of L-type Ca(2+) currents but the molecular determinants responsible for the formation of the heteromeric complex are still being studied. Enzymatic treatment with PI-PLC, a phospholipase C specific for the cleavage of glycosyl-phosphatidylinositol (GPI)-anchored proteins, disrupted plasma membrane localization of the cardiac CaVα2δ1 prompting us to investigate deletions of its hydrophobic transmembrane domain...
May 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28494965/multiscale-determinants-of-delayed-afterdepolarization-amplitude-in-cardiac-tissue
#19
Christopher Y Ko, Michael B Liu, Zhen Song, Zhilin Qu, James N Weiss
Spontaneous calcium (Ca) waves in cardiac myocytes underlie delayed afterdepolarizations (DADs) that trigger cardiac arrhythmias. How these subcellular/cellular events overcome source-sink factors in cardiac tissue to generate DADs of sufficient amplitude to trigger action potentials is not fully understood. Here, we evaluate quantitatively how factors at the subcellular scale (number of Ca wave initiation sites), cellular scale (sarcoplasmic reticulum (SR) Ca load), and tissue scale (synchrony of Ca release in populations of myocytes) determine DAD features in cardiac tissue using a combined experimental and computational modeling approach...
May 9, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28493701/substituted-2-acylamino-cycloalkylthiophene-3-carboxylic-acid-arylamides-as-inhibitors-of-the-calcium-activated-chloride-channel-transmembrane-protein-16a-tmem16a
#20
Eric C Truong, Puay-Wah Phuan, Amanda L Reggi, Loretta Ferrera, Luis J V Galietta, Sarah E Levy, Alannah C Moises, Onur Cil, Elena Diez-Cecilia, Sujin Lee, Alan S Verkman, Marc O Anderson
Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report by screening the discovery of 2-acylamino-cycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A, and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa)...
May 11, 2017: Journal of Medicinal Chemistry
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