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https://www.readbyqxmd.com/read/28526610/11-12-epoxyeicosatrienoic-acid-11-12-eet-reduces-excitability-and-excitatory-transmission-in-the-hippocampus
#1
Nandkishor K Mule, Anette C Orjuela Leon, John R Falck, Michael Arand, Anne Marowsky
Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hippocampus. 11,12 EET (2 μM), but not 14,15 EET (2 μM), induced the opening of a hyperpolarizing K(+) conductance in CA1 pyramidal cells. This action could be blocked by BaCl2, the G protein blocker GDPβ-S and the GIRK1/4 blocker tertiapin Q and the channel was thus identified as a GIRK channel...
May 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28517362/the-absence-of-quadrupolar-nuclei-facilitates-efficient-13-c-hyperpolarization-via-reversible-exchange-with-parahydrogen
#2
Danila A Barskiy, Roman V Shchepin, Christian P N Tanner, Johannes F P Colell, Boyd M Goodson, Thomas Theis, Warren S Warren, Eduard Y Chekmenev
Nuclear spin hyperpolarization techniques are revolutionizing the field of (13) C molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is currently the leading technique, it is generally slow (requiring ≈1 h) and costly (≈$USD10(6) ). As a consequence of carbon's central place in biochemistry, tremendous progress using (13) C d-DNP bioimaging has been demonstrated to date including a number of clinical trials. Despite numerous attempts to develop alternatives to d-DNP, the competing methods have faced significant translational challenges...
May 18, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28515089/the-n-terminus-regulates-voltage-dependent-gating-of-calhm-ion-channels
#3
Jessica E Tanis, Zhongming Ma, J Kevin Foskett
CALHM1 and its C. elegans (ce) homolog, CLHM-1, belong to a new family of physiologically important ion channels that are regulated by voltage and extracellular Ca(2+) (Ca(2+)o), but lack a canonical voltage-sensing domain. Consequently, the intrinsic voltage-dependent gating mechanisms for CALHM channels are unknown. Here, we performed voltage-clamp experiments on ceCLHM-1 chimeric, deletion, insertion and point mutants to assess the role of the N-terminus (NT) in CALHM channel gating. Analyses of chimeric channels in which the ceCLHM-1 and human (h)CALHM1 N-termini were interchanged showed that the hCALHM1 NT destabilized channel-closed states, whereas the ceCLHM-1 NT had a stabilizing effect...
May 17, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28514950/lung-function-imaging-methods-in-cystic-fibrosis-pulmonary-disease
#4
REVIEW
Magdalena Kołodziej, Michael J de Veer, Marian Cholewa, Gary F Egan, Bruce R Thompson
Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis...
May 17, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28511953/small-conductance-ca-2-activated-k-channels-in-the-plasma-membrane-mitochondria-and-the-er-pharmacology-and-implications-in-neuronal-diseases
#5
REVIEW
Birgit Honrath, Inge Krabbendam, Carsten Culmsee, Amalia Dolga
Ca(2+)-activated K(+) (KCa) channels regulate after-hyperpolarization in many types of neurons in the central and peripheral nervous system. Small conductance Ca(2+)-activated K(+) (KCa2/SK) channels, a subfamily of KCa channels, are widely expressed in the central and peripheral nervous system, and in the cardiovascular system. Voltage-independent SK channels are activated by alterations in intracellular Ca(2+) ([Ca(2+)]i) which facilitates the opening of these channels through binding of Ca(2+) to calmodulin that is constitutively bound to the SK2 C-terminus...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28511870/atp-sensitive-k-channels-maintain-resting-membrane-potential-in-interstitial-cells-of-cajal-from-the-mouse-colon
#6
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/28510636/impact-of-aging-on-calcium-signaling-and-membrane-potential-in-endothelium-of-resistance-arteries-a-role-for-mitochondria
#7
Erik J Behringer, Steven S Segal
Impaired blood flow to peripheral tissues during advanced age is associated with endothelial dysfunction and diminished bioavailability of nitric oxide (NO). However, it is unknown whether aging impacts coupling between intracellular calcium ([Ca2+]i) signaling and small- and intermediate K+ channel (SKCa/IKCa) activity during endothelium-derived hyperpolarization (EDH), a signaling pathway integral to dilation of the resistance vasculature. To address the potential impact of aging on EDH, Fura-2 photometry and intracellular recording were applied to evaluate [Ca2+]i and membrane potential of intact endothelial tubes (width, 60 µm; length, 1-3 mm) freshly isolated from superior epigastric arteries of young (4-6 mo) and old (24-26 mo) male C57BL/6 mice...
May 16, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28508552/real-time-analysis-of-folding-upon-binding-of-a-disordered-protein-by-using-dissolution-dnp%C3%A2-nmr-spectroscopy
#8
Mukundan Ragavan, Luigi I Iconaru, Cheon-Gil Park, Richard W Kriwacki, Christian Hilty
The kinase inhibitory domain of the cell cycle regulatory protein p27(Kip1) (p27) was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D-DNP). While intrinsically disordered in isolation, p27 adopts secondary structural motifs, including an α-helical structure, upon binding to cyclin-dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with hyperpolarization enable the real-time observation of (13) C NMR signals during p27 folding upon binding to Cdk2/cyclin A on a time scale of several seconds...
May 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28508450/simultaneous-assessment-of-both-lung-morphometry-and-gas-exchange-function-within-a-single-breath-hold-by-hyperpolarized-129-xe-mri
#9
Jianping Zhong, Huiting Zhang, Weiwei Ruan, Junshuai Xie, Haidong Li, He Deng, Yeqing Han, Xianping Sun, Chaohui Ye, Xin Zhou
During the measurement of hyperpolarized (129) Xe magnetic resonance imaging (MRI), the diffusion-weighted imaging (DWI) technique provides valuable information for the assessment of lung morphometry at the alveolar level, whereas the chemical shift saturation recovery (CSSR) technique can evaluate the gas exchange function of the lungs. To date, the two techniques have only been performed during separate breaths. However, the request for multiple breaths increases the cost and scanning time, limiting clinical application...
May 16, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28507519/vasorelaxing-action-of-the-kynurenine-metabolite-xanthurenic-acid-the-missing-link-in-endotoxin-induced-hypotension
#10
Francesco Fazio, Albino Carrizzo, Luana Lionetto, Antonio Damato, Luca Capocci, Mariateresa Ambrosio, Giuseppe Battaglia, Valeria Bruno, Michele Madonna, Maurizio Simmaco, Ferdinando Nicoletti, Carmine Vecchione
The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28507314/metabolic-imaging-of-energy-metabolism-in-traumatic-brain-injury-using-hyperpolarized-1-13-c-pyruvate
#11
Stephen J DeVience, Xin Lu, Julie Proctor, Parisa Rangghran, Elias R Melhem, Rao Gullapalli, Gary M Fiskum, Dirk Mayer
Traumatic brain injury (TBI) is known to cause perturbations in the energy metabolism of the brain, but current tests of metabolic activity are only indirect markers of energy use or are highly invasive. Here we show that hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) can be used as a direct, non-invasive method for studying the effects of TBI on energy metabolism. Measurements were performed on rats with moderate TBI induced by controlled cortical impact on one cerebral hemisphere. Following injection of hyperpolarized [1-(13)C]pyruvate, the resulting (13)C-bicarbonate signal was found to be 24 ± 6% lower in the injured hemisphere compared with the non-injured hemisphere, while the hyperpolarized bicarbonate-to-lactate ratio was 33 ± 8% lower in the injured hemisphere...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28501215/assessment-of-in-vitro-dopamine-neuroblastoma-cell-interactions-with-a-bioelectric-biosensor-perspective-for-a-novel-in-vitro-functional-assay-for-dopamine-agonist-antagonist-activity
#12
Theofylaktos Apostolou, Georgia Moschopoulou, Evdokia Kolotourou, Spyridon Kintzios
Current receptor-binding assays for dopamine do not measure the in vitro whole cellular response against dopamine or potential agonist/antagonist molecules. We herewith report the development of a novel functional assay concept for studying the in vitro interaction of the neurotransmitter dopamine with neural cells bearing dopamine receptors. The concept is based on the ultra-rapid measurement of changes in the electric properties of cultured N2a mouse neuroblastoma cells (corresponding to cumulative changes of the cell membrane potential)...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28500657/modulation-of-herg-channels-by-5-1h-indazol-5-yl-oxy-methyl-n-4-trifluoromethoxy-phenyl-pyrimidin-2-amine-itp-2-a-novel-small-molecule-activator
#13
Harinath Sale, Samrat Roy, Jayakumar Warrier, Srinivasan Thangathirupathy, Yoganand Vadari, Shruthi K Gopal, Prasad Krishnamurthy, Manjunath Ramarao
BACKGROUND AND PURPOSE: hERG channel activators have potential utility in the treatment of acquired and congenital long QT syndrome. In this article, we describe a new hERG activator, 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), with a chemical structure distinct from the previously reported compounds. EXPERIMENTAL APPROACH: We investigated the effect of ITP-2 on hERG1a and hERG1a/1b channels expressed heterologously in HEK-293 cells using conventional electrophysiological methods...
May 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28499973/activation-of-dopamine-d1-receptors-enhances-the-temporal-summation-and-excitability-of-rat-retinal-ganglion-cells
#14
Peng Cui, Xue-Yan Li, Yuan Zhao, Qian Li, Feng Gao, Ling-Zhu Li, Ning Yin, Xing-Huai Sun, Zhongfeng Wang
Dopamine (DA), an important neurotransmitter and neuromodulator, plays important roles in neuronal physiological functions by activating G-protein-coupled DA D1 and/or D2 receptors. Previous studies have demonstrated that D1 receptors are functionally expressed in retinal neurons and glial cells, including ganglion cells. In this study, we explored the effects of D1 receptor activation on retinal ganglion cell (RGC) temporal summation and excitability in rat retinal slices using electrophysiological techniques...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28497481/harnessing-polarization-transfer-to-indazole-and-imidazole-through-signal-amplification-by-reversible-exchange-to-improve-their-nmr-detectability
#15
Marianna Fekete, Peter J Rayner, Gary G R Green, Simon B Duckett
The Signal Amplification by Reversible Exchange (SABRE) approach has been used to hyperpolarize the substrates indazole and imidazole in the presence of the co-ligand acetonitrile through the action of the precataysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)]. (2) H-labelled forms of these catalysts were also examined. Our comparison of the two pre-catalysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)], coupled with (2) H-labelling of the N-heterocyclic carbene and associated relaxation and polarisation field variation studies demonstrate the critical and collective role these parameters play in controlling the efficiency of SABRE...
May 11, 2017: Magnetic Resonance in Chemistry: MRC
https://www.readbyqxmd.com/read/28496413/cholera-toxin-induces-sustained-hyperexcitability-in-myenteric-but-not-submucosal-ah-neurons-in-guinea-pig-jejunum
#16
Katerina Koussoulas, Rachel M Gwynne, Jaime P P Foong, Joel C Bornstein
Background and Aims: Cholera toxin (CT)-induced hypersecretion requires activation of secretomotor pathways in the enteric nervous system (ENS). AH neurons, which have been identified as a population of intrinsic sensory neurons (ISNs), are a source of excitatory input to the secretomotor pathways. We therefore examined effects of CT in the intestinal lumen on myenteric and submucosal AH neurons. Methods: Isolated segments of guinea pig jejunum were incubated for 90 min with saline plus CT (12.5 μg/ml) or CT + neurotransmitter antagonist, or CT + tetrodotoxin (TTX) in their lumen...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28492229/imaging-of-ph-in-vivo-using-hyperpolarized-13-c-labelled-zymonic-acid
#17
Stephan Düwel, Christian Hundshammer, Malte Gersch, Benedikt Feuerecker, Katja Steiger, Achim Buck, Axel Walch, Axel Haase, Steffen J Glaser, Markus Schwaiger, Franz Schilling
Natural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that (13)C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-(13)C]pyruvic acid and its (13)C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28490495/exclusion-of-alternative-exon-33-of-cav1-2-calcium-channels-in-heart-is-proarrhythmogenic
#18
Guang Li, Juejin Wang, Ping Liao, Peter Bartels, Hengyu Zhang, Dejie Yu, Mui Cheng Liang, Kian Keong Poh, Chye Yun Yu, Fengli Jiang, Tan Fong Yong, Yuk Peng Wong, Zhenyu Hu, Hua Huang, Guangqin Zhang, Mary Joyce Galupo, Jin-Song Bian, Sathivel Ponniah, Scott Lee Trasti, Kelvin See, Roger Foo, Uta C Hoppe, Stefan Herzig, Tuck Wah Soong
Alternative splicing changes the CaV1.2 calcium channel electrophysiological property, but the in vivo significance of such altered channel function is lacking. Structure-function studies of heterologously expressed CaV1.2 channels could not recapitulate channel function in the native milieu of the cardiomyocyte. To address this gap in knowledge, we investigated the role of alternative exon 33 of the CaV1.2 calcium channel in heart function. Exclusion of exon 33 in CaV1.2 channels has been reported to shift the activation potential -10...
May 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28486649/hyperandrogenemia-reduces-endothelium-derived-hyperpolarizing-factor-mediated-relaxation-in-mesenteric-artery-of-female-rats
#19
Jay S Mishra, Amar S More, Gary D V Hankins, Sathish Kumar
Women with polycystic ovary syndrome (PCOS) often present with hyperandrogenemia along with vascular dysfunction and elevated blood pressure. In animal models of PCOS, anti-androgen treatment decreased blood pressure, indicating a key role for androgens in the development of hypertension. However, the underlying androgen-mediated mechanism that contributes to increased blood pressure is not known. This study determined whether elevated androgens affect endothelium-derived hyperpolarizing factor (EDHF)-mediated vascular relaxation responses through alteration in function of gap junctional proteins...
May 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28484627/the-chinchilla-as-a-novel-animal-model-of-pregnancy
#20
Emmeli Mikkelsen, Henrik Lauridsen, Per Mose Nielsen, Haiyun Qi, Thomas Nørlinger, Maria Dahl Andersen, Niels Uldbjerg, Christoffer Laustsen, Puk Sandager, Michael Pedersen
Several parameters are important when choosing the most appropriate animal to model human obstetrics, including gestation period, number of fetuses per gestation and placental structure. The domesticated long-tailed chinchilla (Chinchilla lanigera) is a well-suited and appropriate animal model of pregnancy that often will carry only one offspring and has a long gestation period of 105-115 days. Furthermore, the chinchilla placenta is of the haemomonochorial labyrinthine type and is therefore comparable to the human villous haemomonochorial placenta...
April 2017: Royal Society Open Science
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