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Acid-sensing ion channels

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https://www.readbyqxmd.com/read/28802647/pharmacological-modulation-of-acid-sensing-ion-channels-1a-and-3-by-amiloride-and-2-guanidine-4-methylquinazoline-gmq
#1
Thomas Besson, Eric Lingueglia, Miguel Salinas
Acid-Sensing Ion Channels (ASICs) are cation channels activated by extracellular acidification that emerge as potential pharmacological targets in pain and other neurological disorders. Here, we compare the pharmacological modulation of ASIC1a and ASIC3 channels by amiloride and 2-guanidine-4-methylquinazoline (GMQ), two compounds commonly used for their in vitro and in vivo investigation. We analyzed the effect of amiloride on the pH-dependent activation and inactivation, the relative influence of the extracellular domain and the transmembrane/cytosolic domains on the effect of amiloride and GMQ using chimeras between ASIC1a and ASIC3, and how these compounds potentiate the physiologically relevant ASIC3 sustained window current...
August 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28774677/conorfamide-sr3-a-structurally-novel-specific-inhibitor-of-the-shaker-k-channel
#2
Elba Campos-Lira, Elisa Carrillo, Manuel B Aguilar, Joanna Gajewiak, Froylán Gómez-Lagunas, Estuardo López-Vera
Conorfamides (CNFs) are toxins initially characterized from the venom duct of the venomous marine snail Conus spurius from the Gulf of Mexico; at their C-termini, these toxins are amidated and have high sequence similarity with the molluskan cardioexcitatory tetrapeptide Phe-Met-Arg-Phe-NH2 (FMRFamide or FMRFa) and other FMRFa-related peptides (FaRPs) found in the five molluskan classes, and in other invertebrate and vertebrate phyla. These peptides were the first FaRPs found to be present in any venom, and they are biologically active in mice, limpets, and/or freshwater snails...
July 31, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28768463/molecular-dynamics-simulations-investigate-the-mechanism-of-psalmotoxin-1-regulating-gating-process-of-an-acid-sensing-ion-channel-1a-at-ph-5-5
#3
Hui Yu, Lianjuan Yang, Lu Liu, Xi Zhao, Xuri Huang
Acid-sensing ion channel 1a (ASIC1a) is a cation channel activated by protons and causes neuronal death through central nervous system. Psalmotoxin1 (PcTx1) is a gating modifier for ASIC1a. The process of PcTx1 regulating the channel gating from the extracellular domain to the transmembrane domain is unclear. Here we used molecular dynamics (MD) simulations method to investigate how PcTx1 regulates the gating of the ASIC1a. Our results indicated that PcTx1can mainly regulate ASIC1a gating process through hydrogen bonds, which can affect their relative positions of several key domains in ASIC1a, further, a long-range conformational changes path was determined, which is composed of β1, β2, β10, α6, α7, β11 and β12 in ASIC1a...
August 3, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28765874/upregulation-of-nuclear-factor%C3%A2-%C3%AE%C2%BAb-and-acid-sensing-ion-channel-3-in-dorsal-root-ganglion-following-application-of-nucleus-pulposus-onto-the-nerve-root-in-rats
#4
Dong Wang, Hao Pan, Hang Zhu, Li Zhu, Yong-Jiang He, Jian Wang, Gao-Yong Jia
The nucleus pulposus (NP) is an avascular, hydrated tissue that permits the intervertebral disc to resist compressive loads to the spine. To determine the mechanisms by which intervertebral disc degeneration is caused by the nucleus pulposus, the expression and regulation of nuclear factor (NF)‑κB and acid sensing ion channel 3 (ASIC3) were examined. For the intervertebral disc degeneration model, NP was harvested from the tail of rats and applied to the L5 dorsal root ganglion (DRG). The mechanical pain withdrawal threshold (PWT) in NP model rats was assessed...
July 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28754162/sensitization-of-asic3-by-proteinase-activated-receptor-2-signaling-contributes-to-acidosis-induced-nociception
#5
Jing Wu, Ting-Ting Liu, Yi-Mei Zhou, Chun-Yu Qiu, Ping Ren, Ming Jiao, Wang-Ping Hu
BACKGROUND: Tissue acidosis and inflammatory mediators play critical roles in pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. Extracellular acidosis activates acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced nociception...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28753000/an-easy-to-manufacture-micro-gas-preconcentrator-for-chemical-sensing-applications
#6
Mitchell M McCartney, Yuriy Zrodnikov, Alexander G Fung, Michael K LeVasseur, Josephine M Pedersen, Konstantin Olegovich Zamuruyev, Alexander A Aksenov, Nicholas J Kenyon, Cristina E Davis
We have developed a simple-to-manufacture microfabricated gas preconcentrator for MEMS-based chemical sensing applications. Cavities and microfluidic channels were created using a wet etch process with hydrofluoric acid, portions of which can be performed outside of a cleanroom, instead of the more common deep reactive ion etch process. The integrated heater and resistance temperature detectors (RTDs) were created with a photolithography-free technique enabled by laser etching. With only 28 V DC (0.1 A), a maximum heating rate of 17...
July 28, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28745101/acidosis-counteracts-itch-tachyphylaxis-to-consecutive-pruritogen-exposure-dependent-on-acid-sensing-ion-channel-3
#7
Yi-Ming Jiang, Chen Huang, Zhong Peng, Shao-Ling Han, Wei-Guang Li, Michael Xi Zhu, Tian-Le Xu
Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SL-NH2) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH2 to the same site...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28728821/the-kinetics-and-the-permeation-properties-of-piezo-channels
#8
R Gnanasambandam, P A Gottlieb, F Sachs
Piezo channels are eukaryotic, cation-selective mechanosensitive channels (MSCs), which show rapid activation and voltage-dependent inactivation. The kinetics of these channels are largely consistent across multiple cell types and different stimulation paradigms with some minor variability. No accessory subunits that associate with Piezo channels have been reported. They are homotrimers and each ∼300kD monomer has an N-terminal propeller blade-like mechanosensing module, which can confer mechanosensing capabilities on ASIC-1 (the trimeric non-MSC, acid-sensing ion channel-1) and a C-terminal pore module, which influences conductance, selectivity, and channel inactivation...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28728814/a-tour-de-force-the-discovery-properties-and-function-of-piezo-channels
#9
P A Gottlieb
Mechanical transducers appear throughout cell biology and are used to convert mechanical stress into chemical or electrical signals that allow the cell to respond to environmental changes. In the past six years, a eukaryotic mechanical channel family with two members, Piezo1 and Piezo2, has been identified. Piezo1 was shown to be a cation-selective channel that does not require ancillary proteins for activity. Mouse Piezo1 is large, with over 2500 amino acids, and is not homologous to other ion channels. Both piezo channels have rapid voltage-dependent inactivation with a reversal potential near 0mV...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28725010/glucose-deficiency-elevates-acid-sensing-ion-channel-2a-expression-and-increases-seizure-susceptibility-in-temporal-lobe-epilepsy
#10
Haitao Zhang, Guodong Gao, Yu Zhang, Yang Sun, Huanfa Li, Shan Dong, Wei Ma, Bei Liu, Weiwen Wang, Hao Wu, Hua Zhang
Brain hypometabolism is a common epilepsy-related finding in both patients and animal models. Fluorodeoxyglucose positron emission tomography studies have shown that recurrent seizures lead to reduced glucose metabolism in certain brain regions, but no studies have definitively determined whether this induces epileptogenesis. There is evidence that acid-sensing ion channel 2a (ASIC2a) affects epilepsy susceptibility. Transcription factor CP2 (TFCP2) regulates ASIC2a expression. We report that suppressed TFCP2 expression and elevated ASIC2a expression were associated with glucose hypometabolism in the hippocampi of humans with epilepsy and of rat epilepsy model brains...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718507/gene-expression-analyses-reveal-metabolic-specifications-in-acute-o2-sensing-chemoreceptor-cells
#11
Lin Gao, Victoria Bonilla-Henao, Paula García-Flores, Ignacio Arias-Mayenco, Patricia Ortega-Sáenz, José López-Barneo
Acute O2 sensing is a fundamental property of cells in the peripheral chemoreceptors, e.g. glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM), and is necessary for adaptation to hypoxia. These cells contain O2 -sensitive ion channels, which mediate membrane depolarization and transmitter release upon exposure to hypoxia. However, the mechanisms underlying the detection of changes in O2 tension by cells are still poorly understood. Recently, we suggested that CB glomus cells have specific metabolic features that favour the accumulation of reduced quinone and the production of mitochondrial NADH and reactive oxygen species during hypoxia...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28688766/ligands-of-histamine-receptors-modulate-acid-sensing-ion-channels
#12
V Y Shteinikov, A S Korosteleva, T B Tikhonova, N N Potapieva, D B Tikhonov
Recently we found that synthetic compounds containing amino group linked to hydrophobic or aromatic moiety are potent modulators of the proton-gated channels (ASICs). These structures have clear similarity with ligands of histamine receptors. We have also demonstrated that histamine potentiates homomeric ASIC1a by shifting its activation dependence to less acidic conditions. In the present work the action of a series of histamine receptors ligands on recombinant ASIC1a and ASIC2a was characterized. Two types of action were found for ASIC1a...
September 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28674755/modulation-of-the-fmrfamide-gated-na-channel-by-external-ca-2
#13
Akihiko Fujimoto, Yu Kodani, Yasuo Furukawa
FMRFamide-gated Na(+) channel (FaNaC) is a member of the DEG/ENaC family. Amino acid sequence of the second transmembrane region (TM2) of FaNaC is quite similar to that of the acid-sensing ion channels (ASIC) of the same family. In the upper part of TM2, there are two aspartate residues (D552 and D556 in Aplysia FaNaC, AkFaNaC) which construct two negative rings in the external vestibule. In the present study, we examined the function of D552/D556 mutants of AkFaNaC in Xenopus oocytes with special interest in Ca(2+) sensitivity of FaNaC...
July 3, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28667864/an-acidosis-sparing-ketogenic-ask-diet-to-improve-efficacy-and-reduce-adverse-effects-in-the-treatment-of-refractory-epilepsy
#14
REVIEW
Alan W C Yuen, Isabel A Walcutt, Josemir W Sander
Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets...
June 28, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28657439/elucidating-proton-mediated-conformational-changes-in-an-acid-sensing-ion-channel-1a-through-molecular-dynamics-simulation
#15
Lu Liu, Hui Yu, Lianjuan Yang, Xi Zhao, Xuri Huang
No abstract text is available yet for this article.
June 28, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28657172/asic1a-in-neurons-is-critical-for-fear-related-behaviors
#16
R J Taugher, Y Lu, R Fan, A Ghobbeh, C J Kreple, F M Faraci, J A Wemmie
Acid-sensing ion channels (ASICs) have been implicated in fear-, addiction- and depression-related behaviors in mice. While these effects have been attributed to ASIC1A in neurons, it has been reported that ASICs may also function in nonneuronal cells. To determine if ASIC1A in neurons is indeed required, we generated neuron-specific knockout (KO) mice with floxed Asic1a alleles disrupted by Cre recombinase driven by the neuron-specific synapsin I promoter (SynAsic1a KO mice). We confirmed that Cre expression occurred in neurons, but not all neurons, and not in nonneuronal cells including astrocytes...
June 28, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28655753/the-thermodynamic-basis-of-glucose-stimulated-insulin-release-a-model-of-the-core-mechanism
#17
David F Wilson, Abigail T J Cember, Franz M Matschinsky
A model for glucose sensing by pancreatic β-cells is developed and compared with the available experimental data. The model brings together mathematical representations for the activities of the glucose sensor, glucokinase, and oxidative phosphorylation. Glucokinase produces glucose 6-phosphate (G-6-P) in an irreversible reaction that determines glycolytic flux. The primary products of glycolysis are NADH and pyruvate. The NADH is reoxidized and the reducing equivalents transferred to oxidative phosphorylation by the glycerol phosphate shuttle, and some of the pyruvate is oxidized by pyruvate dehydrogenase and enters the citric acid cycle...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28650315/transient-acidosis-while-retrieving-a-fear-related-memory-enhances-its-lability
#18
Jianyang Du, Margaret P Price, Rebecca J Taugher, Daniel Grigsby, Jamison J Ash, Austin C Stark, Md Zubayer Hossain Saad, Kritika Singh, Juthika Mandal, John A Wemmie, Michael J Welsh
Attenuating the strength of fearful memories could benefit people disabled by memories of past trauma. Pavlovian conditioning experiments indicate that a retrieval cue can return a conditioned aversive memory to a labile state. However, means to enhance retrieval and render a memory more labile are unknown. We hypothesized that augmenting synaptic signaling during retrieval would increase memory lability. To enhance synaptic transmission, mice inhaled CO2 to induce an acidosis and activate acid sensing ion channels...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28636336/a-mg-cp-with-in-situ-encapsulated-photochromic-guest-as-sensitive-fluorescence-sensor-for-fe-3-cr-3-ions-and-nitro-explosives
#19
Zhao-Feng Wu, Liao-Kuo Gong, Xiao-Ying Huang
Here we report a fluorescent magnesium coordination polymer (Mg-CP), namely, [CH3-dpb]2[Mg3(1,4-NDC)4(μ-H2O)2(CH3OH)(H2O)]·1.5H2O (1, 1,4-H2NDC = 1,4-naphthalene dicarboxylic acid, dpb = 1,4-bis(pyrid-4-yl)benzene). Compound 1 possesses a three-dimensional (3D) host-guest structure constructed by the 1,4-NDC linkers bridging the linear trinuclear secondary building units of [Mg3(COO)8(μ-H2O)2]. The dpb molecules were in situ reacted with CH3OH resulting in photochromic cations of [CH3-dpb](+) that acted as guests located in the channels parallel to the b-axis...
June 21, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28618956/acid-sensing-ion-channels-contribute-to-the-effect-of-extracellular-acidosis-on-proliferation-and-migration-of-a549-cells
#20
Yu Wu, Bo Gao, Qiu-Ju Xiong, Yu-Chan Wang, Da-Ke Huang, Wen-Ning Wu
Acid-sensing ion channels, a proton-gated cation channel, can be activated by low extracellular pH and involved in pathogenesis of some tumors such as glioma and breast cancer. However, the role of acid-sensing ion channels in the growth of lung cancer cell is unclear. In this study, we investigated the expression of acid-sensing ion channels in human lung cancer cell line A549 and their possible role in proliferation and migration of A549 cells. The results show that acid-sensing ion channel 1, acid-sensing ion channel 2, and acid-sensing ion channel 3 are expressed in A549 cells at the messenger RNA and protein levels, and acid-sensing ion channel-like currents were elicited by extracellular acid stimuli...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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