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https://www.readbyqxmd.com/read/29740287/inhibition-of-glur-current-in-microvilli-of-sensory-neurons-via-na-microdomain-coupling-among-glur-hcn-channel-and-na-k-pump
#1
Yasuhiro Kawasaki, Mitsuru Saito, Jonghwa Won, Jin Young Bae, Hajime Sato, Hiroki Toyoda, Eriko Kuramoto, Mikihiko Kogo, Takuma Tanaka, Takeshi Kaneko, Seog Bae Oh, Yong Chul Bae, Youngnam Kang
Glutamatergic dendritic EPSPs evoked in cortical pyramidal neurons are depressed by activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels expressed in dendritic spines. This depression has been attributed to shunting effects of HCN current ( I h ) on input resistance or I h deactivation. Primary sensory neurons in the rat mesencephalic trigeminal nucleus (MTN) have the somata covered by spine-like microvilli that express HCN channels. In rat MTN neurons, we demonstrated that I h enhancement apparently diminished the glutamate receptor (GluR) current ( I GluR ) evoked by puff application of glutamate/AMPA and enhanced a transient outward current following I GluR (OT- I GluR )...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29715915/hcn-ppt-level-detection-based-on-a-qepas-sensor-with-amplified-laser-and-a-miniaturized-3d-printed-photoacoustic-detection-channel
#2
Ying He, Yufei Ma, Yao Tong, Xin Yu, Frank K Tittel
Ultra-high sensitive and stable detection of hydrogen cyanide (HCN) based on a quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor was realized using an erbium-doped fiber amplifier (EDFA) as well as a miniaturized 3D-printed photoacoustic detection channel (PADC) for the first time. A HCN molecule absorption line located at 6536.46 cm-1 was selected which was in the range of the EDFA emission spectrum. The detection sensitivity of the reported EDFA-QEPAS sensor was enhanced significantly due to the high available EDFA excitation laser power...
April 16, 2018: Optics Express
https://www.readbyqxmd.com/read/29684576/zd7288-and-mibefradil-inhibit-the-myogenic-heartbeat-in-daphnia-magna-indicating-its-dependency-on-hcn-and-t-type-calcium-ion-channels
#3
Thomas J Pirtle, Troy L Carr, Tanisha Khurana, Grace Meeker
Daphnia magna heartbeat is myogenic-originating within the animal's heart. However, the mechanism for this myogenic automaticity is unknown. The mechanism underlying the automaticity of vertebrate myogenic hearts involves cells (pacemaker cells), which have a distinct set of ion channels that include hyperpolarization activated cyclic nucleotide-gated (HCN) and T-type calcium ion channels. We hypothesized that these ion channels also underlie the automatic myogenic heartbeat of Daphnia magna. The drugs, ZD7288 and mibefradil dihydrochloride, block HCN and T-type calcium ion channels respectively...
April 20, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29667927/biophysics-of-object-segmentation-in-a-collision-detecting-neuron
#4
Richard Burkett Dewell, Fabrizio Gabbiani
Collision avoidance is critical for survival, including in humans, and many species possess visual neurons exquisitely sensitive to objects approaching on a collision course. Here, we demonstrate that a collision-detecting neuron can detect the spatial coherence of a simulated impending object, thereby carrying out a computation akin to object segmentation critical for proper escape behavior. At the cellular level, object segmentation relies on a precise selection of the spatiotemporal pattern of synaptic inputs by dendritic membrane potential-activated channels...
April 18, 2018: ELife
https://www.readbyqxmd.com/read/29621262/rescue-of-hyperexcitability-in-hippocampal-ca1-neurons-from-mecp2-y-mouse-through-surface-potential-neutralization
#5
Saju Balakrishnan, Sergej L Mironov
Hyperventilation is a known feature of Rett syndrome (RTT). However, how hyperventilation is related to other RTT symptoms such as hyperexcitability is unknown. Intense breathing during hyperventilation induces hypocapnia and culminates in respiratory alkalosis. Alkalinization of extracellular milieu can trigger epilepsy in patients who already have neuronal hyperexcitability. By combining patch-clamp electrophysiology and quantitative glutamate imaging, we compared excitability of CA1 neurons of WT and Mecp2 (-/y) mice, and analyzed the biophysical properties of subthreshold membrane channels...
2018: PloS One
https://www.readbyqxmd.com/read/29600831/synthesis-of-densely-packaged-ultrasmall-pt02-clusters-within-a-thioether-functionalised-mof-and-their-catalytic-activity-in-industrial-reactions-at-low-temperature
#6
Marta Mon, Miguel A Rivero-Crespo, Jesús Ferrando-Soria, Alejandro Vidal-Moya, Mercedes Boronat, Antonio Leyva-Pérez, Avelino Corma, Juan C Hernandez-Garrido, Miguel López-Haro, José J Calvino, Giulio Ragazzon, Alberto Credi, Donatella Armentano, Emilio Pardo
The gram-scale synthesis, stabilization and characterization of well-defined ultrasmall subnanometric catalytic clusters on solids represent a challenge. Here, we report the chemical synthesis and X-ray snapshots of Pt20 clusters, homogenously distributed and densely-packaged within the channels of a metal-organic framework. This novel hybrid material catalyzes efficiently, and even most important from an economic and environmental viewpoint, at low temperature (25 to 140 ºC), energetically-costly industrial reactions in the gas phase such as hydrogen cyanide (HCN) production, carbon dioxide (CO2) methanation and alkene hydrogenations...
March 30, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29588962/functional-variants-in-hcn4-and-cacna1h-may-contribute-to-genetic-generalized-epilepsy
#7
Felicitas Becker, Christopher A Reid, Kerstin Hallmann, Han-Shen Tae, A Marie Phillips, Georgeta Teodorescu, Yvonne G Weber, Ailing Kleefuss-Lie, Christian Elger, Edward Perez-Reyes, Steven Petrou, Wolfram S Kunz, Holger Lerche, Snezana Maljevic
Objective: Genetic generalized epilepsy (GGE) encompasses seizure disorders characterized by spike-and-wave discharges (SWD) originating within thalamo-cortical circuits. Hyperpolarization-activated (HCN) and T-type Ca2+ channels are key modulators of rhythmic activity in these brain regions. Here, we screened HCN4 and CACNA1H genes for potentially contributory variants and provide their functional analysis. Methods: Targeted gene sequencing was performed in 20 unrelated familial cases with different subtypes of GGE, and the results confirmed in 230 ethnically matching controls...
September 2017: Epilepsia Open
https://www.readbyqxmd.com/read/29588040/hcn-and-k-2p-channels-in-anesthetic-mechanisms-research
#8
Paul M Riegelhaupt, Gareth R Tibbs, Peter A Goldstein
The ability of a diverse group of agents to produce general anesthesia has long been an area of intense speculation and investigation. Over the past century, we have seen a paradigm shift from proposing that the anesthetized state arises from nonspecific interaction of anesthetics with the lipid membrane to the recognition that the function of distinct, and identifiable, membrane-embedded proteins is dramatically altered in the presence of intravenous and inhaled agents. Among proteinaceous targets, metabotropic and ionotropic receptors garnered much of the attention over the last 30 years, and it is only relatively recently that voltage-gated ion channels have clearly and rigorously been shown to be important molecular targets...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29578948/hcn-channels-contribute-to-spontaneous-activity-in-l4-c-fiber-nociceptors-but-not-a%C3%AE-non-nociceptors-after-axotomy-of-l5-and-inflammation-of-l4-spinal-nervesin-the-rat-in-vivo
#9
Laiche Djouhri, Trevor Smith, Ahmad Ahmeda, Mohammad Alotaibi, Xiechuan Weng
Peripheral neuropathic pain (PNP) associated with partial nerve injury is believed to be driven partly by aberrant spontaneous activity (SA) in both injured and uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are not fully understood, but hyperpolarization-activated cyclic nucleotide gated (HCN) channels which underlie the excitatory Ih current have been implicated in SA generation in axotomized A-fiber neurons following L5-spinal nerve ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with neuroinflammation-inducing chromic-gut, we examined whether HCN channels also contribute to SA in the adjacent L4-neurons...
March 22, 2018: Pain
https://www.readbyqxmd.com/read/29565972/activation-gating-in-hcn2-channels
#10
Sabine Hummert, Susanne Thon, Thomas Eick, Ralf Schmauder, Eckhard Schulz, Klaus Benndorf
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels control electrical rhythmicity in specialized brain and heart cells. We quantitatively analysed voltage-dependent activation of homotetrameric HCN2 channels and its modulation by the second messenger cAMP using global fits of hidden Markovian models to complex experimental data. We show that voltage-dependent activation is essentially governed by two separable voltage-dependent steps followed by voltage-independent opening of the pore. According to this model analysis, the binding of cAMP to the channels exerts multiple effects on the voltage-dependent gating: It stabilizes the open pore, reduces the total gating charge from ~8 to ~5, makes an additional closed state outside the activation pathway accessible and strongly accelerates the ON-gating but not the OFF-gating...
March 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29560633/-effect-of-electroacupuncture-stimulation-of-heart-and-lung-meridians-on-expression-of-myocardial-hcn-2-in-acute-myocardial-ischemia-rats
#11
Zi-Jian Wu, Jie Wang, Wen-Xiu Duan, Chang-Ping Gong, Ling Hu
OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of Heart and Lung meridians on the expression of hyperpolarization-activated cyclic nucleotide gated potassium channel 2 (HCN 2) mRNA and protein in the myocar-dium of the left ventricle in acute myocardial ischemia (AMI) rats, so as to underlying its mechanism in improving ischemic myocardial injury. METHODS: A total of 120 male SD rats were randomly divided into normal control, model, EA-Heart Meridian (HT) and EA-Lung Meridian (LU) groups ( n =30 rats in each group)...
March 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29560119/hcn-channels-contribute-to-the-sensitivity-of-intravenous-anesthetics-in-developmental-mice
#12
Jie Gao, Zhiqiang Hu, Liwei Shi, Na Li, Yeling Ouyang, Shaofang Shu, Shanglong Yao, Xiangdong Chen
It is widely accepted that the induction dose of anesthetics is higher in infants than in adults, although the relevant molecular mechanism remains elusive. We previously showed neuronal hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to hypnotic actions of propofol and ketamine. Interestingly, the expression of HCN channels in neocortex significantly changes during postnatal periods. Thus, we postulated that changes in HCN channels expression might contribute to sensitivity to intravenous anesthetics...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29537030/unimolecular-decomposition-of-formamide-via-direct-chemical-dynamics-simulations
#13
Anchal Gahlaut, Manikandan Paranjothy
Formamide (NH2CHO), being the simplest organic molecule containing an amide functional group, serves as a prototype to study protein and peptide chemistry. Formamide has been found in Comets and interstellar media and its decomposition results in smaller molecules such as NH3, CO, HCN, HNCO, etc. These smaller molecules are considered to have been potential precursors for the formation of complex biological molecules, such as nucleic acids and nucleobases, in the early Earth. Several experimental and theoretical investigations of formamide decomposition have been reported in the literature...
March 28, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29526554/differential-control-of-axonal-and-somatic-resting-potential-by-voltage-dependent-conductances-in-cortical-layer-5-pyramidal-neurons
#14
Wenqin Hu, Bruce P Bean
Voltage-dependent conductances not only drive action potentials but also help regulate neuronal resting potential. We found differential regulation of resting potential in the proximal axon of layer 5 pyramidal neurons compared to the soma. Axonal resting potential was more negative than the soma, reflecting differential control by multiple voltage-dependent channels, including sodium channels, Cav3 channels, Kv7 channels, and HCN channels. Kv7 current is highly localized to the axon and HCN current to the soma and dendrite...
March 21, 2018: Neuron
https://www.readbyqxmd.com/read/29518895/retinal-cyclic-nucleotide-gated-channels-from-pathophysiology-to-therapy
#15
REVIEW
Stylianos Michalakis, Elvir Becirovic, Martin Biel
The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration...
March 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29466436/loss-of-hcn2-leads-to-delayed-gastrointestinal-motility-and-reduced-energy-intake-in-mice
#16
Daniel W Fisher, Phillip Luu, Neha Agarwal, Jonathan E Kurz, Dane M Chetkovich
Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are important regulators of excitability in neural, cardiac, and other pacemaking cells, which are often altered in disease. In mice, loss of HCN2 leads to cardiac dysrhythmias, persistent spike-wave discharges similar to those seen in absence epilepsy, ataxia, tremor, reduced neuropathic and inflammatory pain, antidepressant-like behavior, infertility, and severely restricted growth. While many of these phenotypes have tissue-specific mechanisms, the cause of restricted growth in HCN2 knockout animals remains unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29461059/role-of-dimers-in-the-camp-dependent-activation-of-hyperpolarization-activated-cyclic-nucleotide-modulated-hcn-ion-channels
#17
Bryan VanSchouwen, Giuseppe Melacini
Hyperpolarization-activated cyclic-nucleotide-modulated (HCN) ion channels control rhythmicity in neurons and cardiomyocytes. Cyclic AMP (cAMP) modulates HCN activity through the cAMP-induced formation of a tetrameric gating ring spanning the intracellular region (IR) of HCN. Although evidence from confocal patch-clamp fluorometry indicates that the cAMP-dependent gating of HCN occurs through a dimer of dimers, the structural and dynamical basis of cAMP allostery in HCN dimers has so far remained elusive. Thus, here we examine how dimers influence IR structural dynamics, and the role that such structural dynamics play in HCN allostery...
March 1, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29460132/the-role-of-hcn-channels-in-peristaltic-dysfunction-in-human-ureteral-tuberculosis
#18
Fan He, Zhenxing Yang, Xingyou Dong, Zhenqiang Fang, Qian Liu, Xiaoyan Hu, Shanhong Yi, Longkun Li
OBJECTIVE: To explore the role of HCN channels in ureteral peristaltic dysfunction by comparing the changes in HCN channel levels between normal and tuberculous ureters. METHODS: A total of 32 specimens of human upper ureters were collected by nephrectomy from patients with renal tumor (control group, n = 16) or from patients with renal tuberculosis (experimental group, n = 16); the two groups did not receive radiotherapy, chemotherapy, immunotherapy, or any other special treatment before the surgical procedure...
April 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29444426/inferior-olive-hcn1-channels-coordinate-synaptic-integration-and-complex-spike-timing
#19
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
https://www.readbyqxmd.com/read/29444387/the-structure-of-the-apo-camp-binding-domain-of-hcn4-a-stepping-stone-toward-understanding-the-camp-dependent-modulation-of-the-hyperpolarization-activated-cyclic-nucleotide-gated-ion-channels
#20
REVIEW
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
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