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https://www.readbyqxmd.com/read/28733581/structural-determinants-at-the-m2-muscarinic-receptor-modulate-the-rgs4-girk-response-to-pilocarpine-by-impairment-of-the-receptor-voltage-sensitivity
#1
I-Shan Chen, Kazuharu Furutani, Yoshihisa Kurachi
Membrane potential controls the response of the M2 muscarinic receptor to its ligands. Membrane hyperpolarization increases response to the full agonist acetylcholine (ACh) while decreasing response to the partial agonist pilocarpine. We previously have demonstrated that the regulator of G-protein signaling (RGS) 4 protein discriminates between the voltage-dependent responses of ACh and pilocarpine; however, the underlying mechanism remains unclear. Here we show that RGS4 is involved in the voltage-dependent behavior of the M2 muscarinic receptor-mediated signaling in response to pilocarpine...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733205/-dehydrofukinone-modulates-membrane-potential-and-delays-seizure-onset-by-gabaa-receptor-mediated-mechanism-in-mice
#2
Quelen Iane Garlet, Luana da Costa Pires, Laura Hautrive Milanesi, Joseane Righes Marafiga, Bernardo Baldisserotto, Carlos Fernando de Mello, Berta Maria Heinzmann
(+)-Dehydrofukinone (DHF), isolated from Nectandra grandiflora (Lauraceae) essential oil, induces sedation and anesthesia by modulation of GABAa receptors. However, no study has addressed whether DHF modulates other cellular events involved in the control of cellular excitability, such as seizure behavior. Therefore, the aim of the present study was to investigate the effect of DHF on cellular excitability and seizure behavior in mice. For this purpose, we used isolated nerve terminals (synaptosomes) to examine the effect of DHF on the plasma membrane potential, the involvement of GABAa receptors and the downstream activation of Ca(2+) mobilization...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28731505/calcium-calmodulin-dependent-kinase-2-camkii-mediates-epac-induced-spontaneous-transient-outward-currents-stocs-in-rat-vascular-smooth-muscle
#3
Edward S A Humphries, Tomoko Kamishima, John M Quayle, Caroline Dart
Activation of the major cAMP effector, exchange protein directly activated by cAMP (Epac), induces vascular smooth muscle relaxation by increasing the activity of ryanodine (RyR)-sensitive release channels on the peripheral sarcoplasmic reticulum. Resultant Ca(2+) sparks activate plasma membrane Ca(2+) -activated K(+) (BKCa ) channels, evoking spontaneous transient outward currents (STOCs) that hyperpolarize the cell and reduce voltage-dependent Ca(2+) entry. In this study we investigate the mechanism by which Epac increases STOC activity...
July 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28731153/altered-profile-of-mrna-expression-in-atrioventricular-node-of-streptozotocin%C3%A2-induced-diabetic-rats
#4
Frank Christopher Howarth, Khatija Parekh, Petrilla Jayaprakash, Edward Samuel Inbaraj, Murat Oz, Halina Dobrzynski, Thomas Edward Adrian
Prolonged action potential duration, reduced action potential firing rate, upstroke velocity and rate of diastolic depolarization have been demonstrated in atrioventricular node (AVN) cells from streptozotocin (STZ)‑induced diabetic rats. To further clarify the molecular basis of these electrical disturbances, the mRNA profiles encoding a variety of proteins associated with the generation and conduction of electrical activity in the AVN, were evaluated in the STZ‑induced diabetic rat heart. Expression of mRNA was measured in AVN biopsies using reverse transcription‑quantitative polymerase chain reaction techniques...
July 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28724979/impairment-of-coronary-endothelial-function-by-hypoxia-reoxygenation-involves-trpc3-inhibition-mediated-kca-channel-dysfunction-implication-in-ischemia-reperfusion-injury
#5
Xiang-Chong Wang, Wen-Tao Sun, Jie Fu, Jun-Hao Huang, Cheuk-Man Yu, Malcolm John Underwood, Guo-Wei He, Qin Yang
Despite increasing knowledge of the significance of calcium-activated potassium (KCa) and canonical transient receptor potential (TRPC) channels in endothelial physiology, no studies so far have investigated the link between these two distinct types of channels in the control of vascular tone in pathological conditions. We previously demonstrated that hypoxia-reoxygenation (H-R) inhibits endothelial KCa and TRPC3 channels in porcine coronary arteries (PCAs). The present study further investigated whether modulation of TRPC3 is involved in H-R-induced KCa channel inhibition and associated vasodilatory dysfunction using approaches of wire myography, whole-cell voltage-clamp, and coimmunoprecipitation...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722429/detection-of-k-efflux-from-stimulated-cortical-neurons-by-an-aptamer-modified-silicon-nanowire-field-effect-transistor
#6
Ankur Anand, Chia-Rung Liu, Ai-Chuan Chou, Wan-Hsuan Hsu, Rajesh Kumar Ulaganathan, Yi-Cheng Lin, Chi-An Dai, Fan-Gang Tseng, Chien-Yuan Pan, Yit-Tsong Chen
The concentration gradient of K(+) across the cell membrane of a neuron determines its resting potential and cell excitability. During neurotransmission, the efflux of K(+) from the cell via various channels will not only decrease the intracellular K(+) content but also elevate the extracellular K(+) concentration. However, it is not clear to what extent this change could be. In this study, we developed a multiple-parallel-connected silicon nanowire field-effect transistor (SiNW-FET) modified with K(+)-specific DNA-aptamers (aptamer/SiNW-FET) for the real-time detection of the K(+) efflux from cultured cortical neurons...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722201/susceptibility-induced-distortion-correction-in-hyperpolarized-echo-planar-imaging
#7
Jack J Miller, Angus Z Lau, Damian J Tyler
PURPOSE: Echo planar imaging is an attractive rapid imaging readout that can image hyperpolarized compounds in vivo. By alternating the sign of the phase encoding gradient waveform, spatial offsets arising from uncertain frequency shifts can be determined. We show here that blip-reversed echo planar imaging can also be used to correct for susceptibility and B0 inhomogeneity effects that would otherwise produce image-domain distortion in the heart. METHODS: Previously acquired blip-reversed cardiac 3D-Spectral-Spatial echo planar imaging volumetric timecourses of hyperpolarized [1-(13) C]pyruvate were distortion corrected by a deformation field estimated by reconstructing signal-to-noise ratio (SNR)-weighted progressively subsampled temporally summed images of each metabolite...
July 19, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28719100/deuteration-of-hyperpolarized-%C3%A2-%C3%A2-c-labelled-zymonic-acid-enables-sensitivity-enhanced-dynamic-mri-of-ph
#8
Christian Hundshammer, Stephan Düwel, Simone Köcher, Malte Gersch, Benedikt Feuerecker, Christoph Scheurer, Axel Haase, Steffen J Glaser, Markus Schwaiger, Franz Schilling
Aberrant pH is characteristic of many pathologies such as ischemia, inflammation or cancer. Therefore, a non-invasive and spatially resolved pH determination is valuable for disease diagnosis, characterization of response to treatment and the design of pH-sensitive drug delivery systems. We recently introduced hyperpolarized zymonic acid (ZA) as a novel MRI probe of extracellular pH utilizing dissolution dynamic polarization (DNP) for a more than 10,000-fold NMR signal enhancement. Here we present a strategy to enhance the sensitivity of this approach by deuteration of ZA (ZAd)...
July 18, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28718822/a-bacterial-toxin-with-analgesic-properties-hyperpolarization-of-drg-neurons-by-mycolactone
#9
Ok-Ryul Song, Han-Byul Kim, Samuel Jouny, Isabelle Ricard, Alexandre Vandeputte, Nathalie Deboosere, Estelle Marion, Christophe J Queval, Pierre Lesport, Emmanuel Bourinet, Daniel Henrion, Seog Bae Oh, Guillaume Lebon, Guillaume Sandoz, Edouard Yeramian, Laurent Marsollier, Priscille Brodin
Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization...
July 18, 2017: Toxins
https://www.readbyqxmd.com/read/28716678/cancer-recurrence-monitoring-using-hyperpolarized-1-13-c-pyruvate-metabolic-imaging-in-murine-breast-cancer-model
#10
Peter J Shin, Zihan Zhu, Roman Camarda, Robert A Bok, Alicia Y Zhou, John Kurhanewicz, Andrei Goga, Daniel B Vigneron
The purpose of this work was to study the anatomic and metabolic changes that occur with tumor progression, regression and recurrence in a switchable MYC-driven murine breast cancer model. Serial (1)H MRI and hyperpolarized [1-(13)C]pyruvate metabolic imaging were used to investigate the changes in tumor volume and glycolytic metabolism over time during the multistage tumorigenesis. We show that acute de-induction of MYC expression in established tumors results in rapid tumor regression and significantly reduced glycolytic metabolism as measured by pyruvate-to-lactate conversion...
July 14, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28714674/characterization-of-chemical-exchange-using-relaxation-dispersion-of-hyperpolarized-nuclear-spins
#11
Mengxiao Liu, Yaewon Kim, Christian Hilty
Chemical exchange phenomena are ubiquitous in macromolecules, which undergo conformational change or ligand complexation. NMR relaxation dispersion (RD) spectroscopy based on a Carr-Purcell-Meiboom-Gill pulse sequence is widely applied to identify the exchange and measure the life time of intermediate states on the millisecond time scale. Advances in hyperpolarization methods improve the applicability of NMR spectroscopy when rapid acquisitions or low concentrations are required, through an increase in signal strength by several orders of magnitude...
July 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28714121/acetylcholine-dependent-upregulation-of-task-1-channels-in-thalamic-interneurons-by-a-smooth-muscle-like-signalling-pathway
#12
Michael Leist, Susanne Rinné, Maia Datunashvili, Ania Aissaoui, Hans-Christian Pape, Niels Decher, Sven G Meuth, Thomas Budde
The dorsal part of the lateral geniculate nucleus (dLGN) is the main thalamic site for state-dependent transmission of visual information. Non-retinal inputs from the ascending arousal system and inhibition provided by γ-aminobutyric acid (GABA)ergic local circuit interneurons (INs) control neuronal activity within the dLGN. In particular, acetylcholine (ACh) depolarizes thalamocortical relay (TC) neurons by inhibiting two-pore domain potassium (K2P ) channels. Conversely, ACh also hyperpolarizes INs via an as-yet-unknown mechanism...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28713290/advanced-maternal-age-worsens-postpartum-vascular-function
#13
Jude S Morton, Alison S Care, Raven Kirschenman, Christy-Lynn Cooke, Sandra T Davidge
The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years. Aging also independently increases the risk of cardiovascular disease; therefore, combined risk in women of advanced maternal age may lead to detrimental cardiovascular outcomes later in life...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28708395/dynamic-nuclear-polarization-of-long-lived-nuclear-spin-states-in-methyl-groups
#14
Jean-Nicolas Dumez, Basile Vuichoud, Daniele Mammoli, Aurélien Bornet, Arthur C Pinon, Gabriele Stevanato, Benno Meier, Geoffrey Bodenhausen, Sami Jannin, Malcolm H Levitt
We have induced hyperpolarized long-lived states in compounds containing 13C-bearing methyl groups by dynamic nuclear polarization (DNP) at cryogenic temperatures, followed by dissolution with a warm solvent. The hyperpolarized methyl long-lived states give rise to enhanced antiphase 13C NMR signals in solution, which often persist for times much longer than the 13C and 1H spin-lattice relaxation times under the same conditions. The DNP-induced effects are similar to quantum-rotor-induced-polarization (QRIP), but are observed in a wider range of compounds, since they do not depend critically on the height of the rotational barrier...
July 14, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28708304/hyperpolarized-13-c-magnetic-resonance-evaluation-of-renal-ischemia-reperfusion-injury-in-a-murine-model
#15
Celine Baligand, Hecong Qin, Aisha True-Yasaki, Jeremy W Gordon, Cornelius von Morze, Justin Delos Santos, David M Wilson, Robert Raffai, Patrick M Cowley, Anthony J Baker, John Kurhanewicz, David H Lovett, Zhen Jane Wang
Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) (13) C dehydroascorbate (DHA) and (13) C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI)...
July 14, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28707963/in-vivo-assessment-of-ovarian-tumor-response-to-tyrosine-kinase-inhibitor-pazopanib-by-using-hyperpolarized-13-c-pyruvate-mr-spectroscopy-and-18-f-fdg-pet-ct-imaging-in-a-mouse-model
#16
Murali K Ravoori, Sheela P Singh, Jaehyuk Lee, James A Bankson, Vikas Kundra
Purpose To assess in a mouse model whether early or late components of glucose metabolism, exemplified by fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and hyperpolarized carbon 13 ((13)C)-pyruvate magnetic resonance (MR) spectroscopy, can serve as indicators of response in ovarian cancer to multityrosine kinase inhibitor pazopanib. Materials and Methods In this Animal Care and Use Committee approved study, 17 days after the injection of 2 × 10(6) human ovarian SKOV3 tumors cells into 14 female nude mice, treatment with vehicle or pazopanib (2...
July 13, 2017: Radiology
https://www.readbyqxmd.com/read/28705737/leptin-regulation-of-inward-membrane-currents-electrical-activity-and-lh-release-in-isolated-bovine-gonadotropes
#17
Belisario Domínguez-Mancera, Manuel Barrientos-Morales, Patricia Cervantes-Acosta, Antonio Hernández-Beltrán, Araceli Rodríguez-Andrade, Ricardo González-Ramírez, Eduardo Monjaraz, Ricardo Felix
Leptin, a peptide hormone produced by adipocytes, is recognized as one of the signals involved in the onset of reproductive activity. The leptin receptor has been found in hypothalamic neurons and pituitary gonadotropes, suggesting that the hormone may act at both sites to stimulate the secretion of GnRH and consequently, FSH and LH. In response to a stimulus such as a hypothalamic secretagogue, gonadotropes respond with changes in electrical activity, intracellular Ca(2+) and hormone release. The main aim of this report was to investigate whether leptin promotes a change in the electrical and secretory activities of bovine gonadotropes...
July 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28702127/coordinating-heart-morphogenesis-a-novel-role-for-hyperpolarization-activated-cyclic-nucleotide-gated-hcn-channels-during-cardiogenesis-in-xenopus-laevis
#18
Emily Pitcairn, Hannah Harris, Justine Epiney, Vaibhav P Pai, Joan M Lemire, Bin Ye, Nian-Qing Shi, Michael Levin, Kelly A McLaughlin
Hyperpolarization-activated cyclic-nucleotide gated channel (HCN) proteins are important regulators of both neuronal and cardiac excitability. Among the 4 HCN isoforms, HCN4 is known as a pacemaker channel, because it helps control the periodicity of contractions in vertebrate hearts. Although the physiological role of HCN4 channel has been studied in adult mammalian hearts, an earlier role during embryogenesis has not been clearly established. Here, we probe the embryonic roles of HCN4 channels, providing the first characterization of the expression profile of any of the HCN isoforms during Xenopus laevis development and investigate the consequences of altering HCN4 function on embryonic pattern formation...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28701928/the-hyperpolarization-activated-current-determines-synaptic-excitability-calcium-activity-and-specific-viability-of-substantia-nigra-dopaminergic-neurons
#19
Carmen Carbone, Alessia Costa, Gustavo Provensi, Guido Mannaioni, Alessio Masi
Differential vulnerability between Substantia Nigra pars compacta (SNpc) and Ventral Tegmental Area (VTA) dopaminergic (DAergic) neurons is a hallmark of Parkinson's disease (PD). Understanding the molecular bases of this key histopathological aspect would foster the development of much-needed disease-modifying therapies. Non-heterogeneous DAergic degeneration is present in both toxin-based and genetic animal models, suggesting that cellular specificity, rather than causing factors, constitutes the background for differential vulnerability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28698388/delayed-cryptochrome-degradation-asymmetrically-alters-the-daily-rhythm-in-suprachiasmatic-clock-neuron-excitability
#20
Sven Wegner, Mino D C Belle, Alun T L Hughes, Casey O Diekman, Hugh D Piggins
Suprachiasmatic nuclei (SCN) neurons contain an intracellular molecular circadian clock and the Cryptochromes (CRY1/2), key transcriptional repressors of this molecular apparatus, are subject to post-translational modification through ubiquitination and targeting for proteosomal degradation by the ubiquitin E3 ligase complex. Loss-of-function point mutations in a component of this ligase complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and lengthen the circadian period by ∼2.5h...
July 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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