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Derek L F Garden, Marlies Oostland, Marta Jelitai, Arianna Rinaldi, Ian Duguid, Matthew F Nolan
Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the inferior olive (IO), are critical for motor coordination, and are central to theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels expressed by IO neurons have been considered as pacemaker currents important for oscillatory and resonant dynamics. Here, we demonstrate that in vitro, network actions of HCN1 channels enable bidirectional glutamatergic synaptic responses, while local actions of HCN1 channels determine the timing and waveform of synaptically driven action potentials...
February 13, 2018: Cell Reports
Madoka Akimoto, Bryan VanSchouwen, Giuseppe Melacini
The hyperpolarization-activated cyclic-nucleotide-gated (HCN) ion channels control nerve impulse transmission and cardiac pacemaker activity. The modulation by cAMP is critical for the regulatory function of HCN in both neurons and cardiomyocytes, but the underlying mechanism is not fully understood. Here, we show how the structure of the apo cAMP-binding domain of the HCN4 isoform has contributed to a model for the cAMP-dependent modulation of the HCN ion-channel. This model recapitulates the structural and dynamical changes that occur along the thermodynamic cycle arising from the coupling of cAMP-binding and HCN self-association equilibria...
February 14, 2018: FEBS Journal
Andrew S Bohannon, John J Hablitz
Layer 1 (L1) interneurons (INs) play a key role in modulating the integration of inputs to pyramidal neurons (PNs) and controlling cortical network activity. Hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN) channels are known to alter the intrinsic and synaptic excitability of principal components (PCs) as well as select populations of GABAergic INs. However, the developmental profile and functional role of HCN channels in diverse L1 IN populations is not completely understood...
2018: Frontiers in Cellular Neuroscience
Qian Liu, Chao Wu, Shengquan Huang, Qingjian Wu, Tao Zhou, Xiaobing Liu, Xin Liu, Xiaoyan Hu, Longkun Li
Spinal cord injury (SCI) leads to bereft voluntary control of bladder, but the possible role of spontaneous excited system in bladder of SCI patients is poorly understood. Hyper-polarization-activated cyclic nucleotide-gated (HCN) channels are deemed to regulate the spontaneous contraction of bladder, our study explored the functional role of HCN channels in SCI induced neurogenic bladder. Sixty female Sprague-Dawley rats were randomized into control, sham and SCI groups. Rat models subjected to SCI at S2 levels were successfully established and were assessed using hematoxylin and eosin staining and cystometry...
February 13, 2018: International Journal of Molecular Medicine
Patricia Monteiro
Autism, from the Greek autos ("self") and ismos ("action") was initially described as a congenital lack of interest in other people. This article is protected by copyright. All rights reserved.
February 10, 2018: Journal of Physiology
Federica Frigerio, Corey Flynn, Ye Han, Kyle Lyman, Joaquin N Lugo, Teresa Ravizza, Antoine Ghestem, Julika Pitsch, Albert Becker, Anne E Anderson, Annamaria Vezzani, Dane Chetkovich, Christophe Bernard
Neuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long-lasting inflammatory response in hippocampal microglia associated with a concomitant upregulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic AMP-gated channel type 1 (HCN1) protein level while Kv4...
February 9, 2018: Molecular Neurobiology
M Cherif, B Valenti, S Abidi, G Luciano, S Mattioli, M Pauselli, I Bouzarraa, A Priolo, H Ben Salem
Twenty-eight Barbarine male lambs were used to investigate the effect of dietary Nigella sativa seeds (NSS) on meat fatty acids and oxidative stability in two different feeding systems (high- or low-concentrate). Dietary treatments were planned to offer: 70% barley hay and 30% concentrate (LC); LC+12g/day of NSS (LCN); 30% barley hay and 70% concentrate (HC); HC+12g/day of NSS (HCN). NSS increased intramuscular fat only in the low-concentrate system (P=0.039); accordingly, the content of 14:0, c-9 14:1, t-9 18:1, t-11 18:1 and both individual and sum of odd and branched chain fatty acids were greater in LCN than LC meat...
February 2, 2018: Meat Science
Kuihao Chen, Dongchuan Zuo, Sho-Ya Wang, Haijun Chen
Spontaneous rhythmic action potential or pacemaking activity of pacemaker cells controls rhythmic signaling such as heartbeat. The mechanism underlying the origin of pacemaking activity is not well understood. In this study, we created human embryonic kidney (HEK) 293 cells that show pacemaking activity through heterologous expression of strong inward rectifier K+ channels (Kir2.1), hyperpolarization-activated cyclic nucleotide-gated nonselective cation channels (HCN2), and voltage-gated Na+ or Ca2+ channels (Nav1...
January 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Anurag Srivastava, Priya Gupta, Md Shahzad Khan, Mohammed Benali Kanoun, Souraya Goumri-Said
The present paper reports the analysis of surface decoration on the structural, electronic, and optical properties of (n,0) ZnO nanotubes, performed by means of a density function theory based ab-initio approach. Fe functionalization induced buckling in ZnO nanotubes affects its electronic and optical properties. Increase in Fe functionalization leads to better stability of ZnO nanotube and shows enhanced metallic character. The possibility of its use in optoelectronics has been analyzed in terms of dielectric constant, absorption coefficient, and refractive index...
February 4, 2018: Journal of Molecular Modeling
Hsing-Jung Lai, Chien-Lin Chen, Li-Kai Tsai
Objective The pathophysiology of spinal muscular atrophy (SMA) is still unclear. Methods The nerve excitability test in SMA patients and a mouse model of SMA was carried out to explore the pathophysiology of nodal and internodal currents, and quantitative PCR, Western blotting and whole-cell patch-clamp recording were used for the identified hypothesis. Results The nerve excitability test in SMA patients showed increased inward rectification in the current-threshold relationship and increased overshoot after hyperpolarizing threshold electrotonus, which indicates increased hyperpolarization-activated cyclic nucleotide-gated (HCN) current; these findings correlated with disease severity...
February 2, 2018: Annals of Neurology
Liqiang Liu, Xiaowei Zhang, Chengrui Nan, Zongmao Zhao, Shucheng Ma, Wenhua Li, Hongchao Hu, Zhaohui Liang
Glioblastoma (GBM) is an incurable cancer, with mean post-diagnosis survival time of 14-16 months. Metagenomic analysis by The Cancer Genome Atlas (TCGA) program has identified microRNA-182-5p (miR-182-5p or miR-182) as the only miRNA associated with favorable disease prognosis and temozolomide (TMZ) susceptibility. Previous reports have indicated that miR-182 down regulates expression of BCL2L12, c-MET, and HIF2A. However, other messenger RNA (mRNA) targets of miR-182 have not been validated which would explain its association with a favorable disease prognosis...
December 29, 2017: Oncotarget
Dirk Weihrauch, Garett Joseph, Patrick Allen
Invertebrates employ a variety of ammonia excretion strategies to facilitate their survival in diverse aquatic environments, including freshwater, seawater and the water film surrounding soil particles. Various environmental properties set innate challenges for an organism's ammonia excretory capacity. These include the availability of NaCl and the respective ion-permeability of the organism's transport epithelia, and the buffering capacity of their immediate surrounding medium. To this end, some transporters seem to be conserved in the excretory process...
January 29, 2018: Journal of Experimental Biology
Surajit Nandi, Debankur Bhattacharyya, Anakuthil Anoop
The HCN oligomerization is considered to be one of the important pathways in the chemical evolution. Nucleobases, aminoacids and many other complex organic molecules can be evolved through this pathway. We report an explorative study based on automated reaction search method that avoid the cognitive bias in searching the chemical reaction space. We have discussed the chemical space of HCN dimer elaborately, and the important trimers and tetramers are discussed briefly. A component wise molecular fingerprint based methodology is proposed for identifying molecular similarity...
January 25, 2018: Chemistry: a European Journal
Weihua Ding, Zerong You, Shiqian Shen, Jinsheng Yang, Lim Grewo, Jason T Doheny, Shengmei Zhu, Yi Zhang, Lucy Chen, Jianren Mao
Orofacial neuropathic pain caused by trigeminal nerve injury is a debilitating condition with limited therapeutic options. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability and are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the gasserian ganglion on trigeminal neuropathic pain has not been examined. We evaluated nociceptive behaviors after microinjection of the HCN channel blockers ZD7288 or ivabradine into the gasserian ganglion in rats with trigeminal nerve injury...
January 20, 2018: Journal of Pain: Official Journal of the American Pain Society
Stephanie Hans, Alex R Quijada-Rodriguez, Garett J P Allen, Horst Onken, Jason R Treberg, Dirk Weihrauch
Many studies have investigated ammonia excretion and acid-base regulation in aquatic arthropods, yet current knowledge of marine chelicerates is non-existent. In American horseshoe crabs (Limulus polyphemus), book gills bear physiologically distinct regions: dorsal and ventral half-lamellae, and central mitochondria-rich (CMRA) and peripheral mitochondria-poor areas (PMPA). CMRA and ventral half-lamella exhibited characteristics important to ammonia excretion and/or acid-base regulation as supported by high expression levels of Rhesus-protein 1 (LpRh-1), cytoplasmic carbonic anhydrase (CA-2), and hyperpolarization-activated cyclic nucleotide-gated K+ channel (HCN) compared to PMPA and dorsal half-lamella...
January 18, 2018: Journal of Experimental Biology
Sheng-Tao Yang, Min Wang, Constantinos D Paspalas, Johanna L Crimins, Marcus T Altman, James A Mazer, Amy F T Arnsten
Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons...
January 17, 2018: Cerebral Cortex
S S Rudel, C Pietzonka, M Hoelzel, F Kraus
The reaction of uranium tetrachloride with anhydrous liquid hydrogen cyanide yields a turquoise microcrystalline powder of tetrachloridotetraformonitrileuranium(iv), [UCl4(HCN)4]. We determined the crystal structure of this compound by powder neutron diffraction. The compound was further characterized by IR spectroscopy and thermogravimetric analysis as well as by magnetic measurements. The paramagnetic compound crystallizes in the tetragonal space group type I4[combining macron]. To the best of our knowledge this compound represents the first structurally elucidated uranium(iv) complex with HCN as a ligand...
January 17, 2018: Chemical Communications: Chem Comm
F Resta, L Micheli, A Laurino, V Spinelli, T Mello, L Sartiani, L Di Cesare Mannelli, E Cerbai, C Ghelardini, M N Romanelli, G Mannaioni, A Masi
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies...
January 12, 2018: Neuropharmacology
Lingliang Long, Meiyu Huang, Ning Wang, Yanjun Wu, Kun Wang, Aihua Gong, Zhijian Zhang, Jonathan L Sessler
An ability to visualize HCN in mitochondria in real time may permit additional insights into the critical toxicological and physiological roles this classic toxin plays in living organ-isms. Herein, we report a mitochondria-specific coumarin pyrrolidinium-derived fluorescence probe (MRP1) that permits the real time ratiometric imaging of HCN in living cells. The response is specific, sensitive (detection limit is ca. 65.6 nM), rapid (within 1 s), and reversible. Probe MRP1 contains a ben-zyl chloride subunit designed to enhance retention within the mitochondria under conditions where the mitochondria membrane potential is eliminated...
January 16, 2018: Journal of the American Chemical Society
Carsten Bolm, Rita Mocci, Christian Schumacher, Mathias Turberg, Francesco Puccetti, José G Hernández
Mechanochemical activation of iron cyano complexes by ball milling results in the formation of HCN, which can be trapped and incorporated into α-aminonitriles. This prebiotic impact scenario can be extended by mechanochemically transforming the resulting α-aminonitriles into α-amino amides using a chemical route related to early Earth conditions.
January 15, 2018: Angewandte Chemie
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