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https://www.readbyqxmd.com/read/29351585/core-differences-in-synaptic-signaling-between-primary-visual-and-dorsolateral-prefrontal-cortex
#1
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
https://www.readbyqxmd.com/read/29339292/selective-hcn1-block-as-a-strategy-to-control-oxaliplatin-induced-neuropathy
#2
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
https://www.readbyqxmd.com/read/29327340/shank3-deficient-thalamocortical-neurons-show-hcn-channelopathy-and-alterations-in-intrinsic-electrical-properties
#3
Mengye Zhu, VinayKumar Idikuda, Jianbing Wang, Fusheng Wei, Virang Kumar, Nikhil Shah, Christopher B Waite, Qinglian Liu, Lei Zhou
Shank3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in Shank3 gene have been linked to neuropsychiatric disorders especially the Autism Spectrum Disorders (ASD). Shank3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different Shank3 isoforms, Shank3A and Shank3C, significant increase the surface expression of the hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel...
January 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29288034/structural-and-functional-remodelling-of-the-atrioventricular-node-with-ageing-in-rats-the-role-of-hyperpolarization-activated-cyclic-nucleotide-gated-and-ryanodine-2-channels
#4
Yawer Saeed, Ian Temple, Zoltan Borbas, Andrew Atkinson, Joseph Yanni, Michal Maczewski, Urszula Mackiewicz, Mariam Aly, Sunil J R J Logantha, Clifford Garratt, Halina Dobrzynski
BACKGROUND: Ageing is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVES: The aim of the study is to identify the structural and functional remodelling in the atrioventricular junction (AVJ) with ageing. METHODS: Electrophysiological, histology and immunohistochemistry experiments on male Wistar-Hanover rats aged 3months (n=24) and 2years (n=15) were performed. AH interval, Wenkebach cycle length (WBCL) and AVN effective refractory period (AVNERP) were measured...
December 26, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29282531/kir2-1-channels-set-two-levels-of-resting-membrane-potential-with-inward-rectification
#5
Kuihao Chen, Dongchuan Zuo, Zheng Liu, Haijun Chen
Strong inward rectifier K+ channels (Kir2.1) mediate background K+ currents primarily responsible for maintenance of resting membrane potential. Multiple types of cells exhibit two levels of resting membrane potential. Kir2.1 and K2P1 currents counterbalance, partially accounting for the phenomenon of human cardiomyocytes in subphysiological extracellular K+ concentrations or pathological hypokalemic conditions. The mechanism of how Kir2.1 channels contribute to the two levels of resting membrane potential in different types of cells is not well understood...
December 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29239349/influences-of-ivabradine-treatment-on-serum-levels-of-cardiac-biomarkers-sst2-gdf-15-supar-and-h-fabp-in-patients-with-chronic-heart-failure
#6
Peter Jirak, Dzeneta Fejzic, Vera Paar, Bernhard Wernly, Rudin Pistulli, Ilonka Rohm, Christian Jung, Uta C Hoppe, P Christian Schulze, Michael Lichtenauer, Atilla Yilmaz, Daniel Kretzschmar
Chronic heart failure (CHF) represents a major cause of hospitalization and death. Recent evidence shows that novel biomarkers such as soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) are correlated with inflammatory and ischemic responses in CHF patients. In this study we examined the effects of Ivabradine that inhibited the hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel, also called funny current If), thereby leading to selective heart rate reduction and improved myocardial oxygen supply on the cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in 50 CHF patients at the University Hospital of Jena...
December 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29233886/structural-insights-into-the-mechanisms-of-cnbd-channel-function
#7
REVIEW
Zachary M James, William N Zagotta
Cyclic nucleotide-binding domain (CNBD) channels are a family of ion channels in the voltage-gated K+ channel superfamily that play crucial roles in many physiological processes. CNBD channels are structurally similar but functionally very diverse. This family includes three subfamilies: (1) the cyclic nucleotide-gated (CNG) channels, which are cation-nonselective, voltage-independent, and cyclic nucleotide-gated; (2) the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are weakly K+ selective, hyperpolarization-activated, and cyclic nucleotide-gated; and (3) the ether-à-go-go-type (KCNH) channels, which are strongly K+ selective, depolarization-activated, and cyclic nucleotide-independent...
December 12, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29225577/if-channel-as-an-emerging-therapeutic-target-for-cardiovascular-diseases-a-review-of-current-evidence-and-controversies
#8
REVIEW
Hayelom G Mengesha, Tadesse B Tafesse, Mohammed H Bule
In 2015, non-communicable diseases accounted for 39.5 million (70%) of the total 56.4 million deaths that occurred globally, of which 17.7 million (45%) were due to cardiovascular diseases. An elevated heart rate is considered to be one of the independent predictors and markers of future cardiovascular diseases. A variety of experimental and epidemiological studies have found that atherosclerosis, heart failure, coronary artery disease, stroke, and arrhythmia are linked to elevated heart rate. Although there are established drugs to reduce the heart rate, these drugs have undesirable side effects...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29209170/noradrenaline-modulates-the-membrane-potential-and-holding-current-of-medial-prefrontal-cortex-pyramidal-neurons-via-%C3%AE-1-adrenergic-receptors-and-hcn-channels
#9
Katarzyna Grzelka, Przemysław Kurowski, Maciej Gawlak, Paweł Szulczyk
The medial prefrontal cortex (mPFC) receives dense noradrenergic projections from the locus coeruleus. Adrenergic innervation of mPFC pyramidal neurons plays an essential role in both physiology (control of memory formation, attention, working memory, and cognitive behavior) and pathophysiology (attention deficit hyperactivity disorder, posttraumatic stress disorder, cognitive deterioration after traumatic brain injury, behavioral changes related to addiction, Alzheimer's disease and depression). The aim of this study was to elucidate the mechanism responsible for adrenergic receptor-mediated control of the resting membrane potential in layer V mPFC pyramidal neurons...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29168010/modulation-of-thalamocortical-oscillations-by-trip8b-an-auxiliary-subunit-for-hcn-channels
#10
Mehrnoush Zobeiri, Rahul Chaudhary, Maia Datunashvili, Robert J Heuermann, Annika Lüttjohann, Venu Narayanan, Sabine Balfanz, Patrick Meuth, Dane M Chetkovich, Hans-Christian Pape, Arnd Baumann, Gilles van Luijtelaar, Thomas Budde
Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, I h, in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I h current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b(-/-))...
November 22, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29163060/nmda-receptors-regulate-the-development-of-neuronal-intrinsic-excitability-through-cell-autonomous-mechanisms
#11
Guoqiang Hou, Zhong-Wei Zhang
Maturation of neuronal and synaptic functions during early life is essential for the development of neuronal circuits and behaviors. In newborns synaptic transmission at excitatory synapses is primarily mediated by N-methyl-D-aspartate receptors (NMDARs), and NMDAR-mediated signaling plays an important role in synaptic maturation. Concomitant with synapse development, the intrinsic properties of neurons undergo dramatic changes during early life. However, little is known about the role of NMDARs in the development of intrinsic excitability...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29094305/noradrenergic-fiber-sprouting-and-altered-transduction-in-neuropathic-prefrontal-cortex
#12
Steven Cordeiro Matos, Maria Zamfir, Geraldine Longo, Alfredo Ribeiro-da-Silva, Philippe Séguéla
Functional changes in hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels have been shown to contribute to medial prefrontal (mPFC) hyperexcitability after peripheral nerve injury. A reduction in the open probability of these neuronal channels might be relevant since this can enhance membrane input resistance and synaptic summation. However, the molecular mechanisms underlying neuropathy-associated alterations in HCN channel activity remain elusive. Using the spared nerve injury model of neuropathic pain in Long-Evans rats, we first discovered a significant increase in noradrenergic innervation within the mPFC of nerve-injured compared to control animals...
November 1, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29064616/gain-of-function-hcn2-variants-in-genetic-epilepsy
#13
Melody Li, Snezana Maljevic, A Marie Phillips, Slave Petrovski, Michael Hildebrand, Rosemary Burgess, Therese Mount, Federico Zara, Pasquale Striano, Julian Schubert, Holger Thiele, Peter Nürnberg, Michael Wong, Judith L Weisenberg, Liu Lin Thio, Holger Lerche, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou, Christopher A Reid
Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes...
October 24, 2017: Human Mutation
https://www.readbyqxmd.com/read/29054409/dual-expression-of-constitutively-active-g%C3%AE-s-protein-coupled-receptors-differentially-establishes-the-resting-activity-of-the-camp-gated-hcn2-channel-in-a-single-compartment
#14
Noriyuki Nakashima, Kie Nakashima, Takeo Nakayama, Akiko Takaku, Ryosuke Kanamori
The hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channel is a major subtype of the HCN channel family expressed in the nervous system that sets the membrane potential, regulates cell excitability and senses changes in the extracellular environment. Neurons express various Gαs-protein-coupled receptors (GPCRs), many of which show ligand-independent constitutive activity. These membrane-bound proteins are expressed in various subcellular compartments of neurons. Therefore, some proportion of HCN2 channels opens in response to the basal cAMP pool size produced by constitutively active GPCRs...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28973319/differential-effects-of-hcn-channel-block-on-on-and-off-pathways-in-the-retina-as-a-potential-cause-for-medication-induced-phosphene-perception
#15
Sebastian Bemme, Michael Weick, Tim Gollisch
Purpose: Phosphene perception is a characteristic side effect of heart rate-reducing medication that acts on hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. It is hypothesized that these phosphenes are caused by blocking HCN channels in photoreceptors and neurons of the retina, yet the underlying changes in visual signal processing in the retina caused by the HCN channel block are still unknown. Methods: We examined the effects of pharmacologic HCN channel block on the encoding of visual signals in retinal ganglion cells by recording ganglion cell spiking activity from isolated mouse retinas mounted on multielectrode arrays...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28957668/aldosterone-sensing-neurons-in-the-nts-exhibit-state-dependent-pacemaker-activity-and-drive-sodium-appetite-via-synergy-with-angiotensin-ii-signaling
#16
Jon M Resch, Henning Fenselau, Joseph C Madara, Chen Wu, John N Campbell, Anna Lyubetskaya, Brian A Dawes, Linus T Tsai, Monica M Li, Yoav Livneh, Qingen Ke, Peter M Kang, Géza Fejes-Tóth, Anikó Náray-Fejes-Tóth, Joel C Geerling, Bradford B Lowell
Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTSHSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTSHSD2 neuron activation, identify the circuit by which NTSHSD2 neurons drive appetite, and uncover an interaction between the NTSHSD2 circuit and ATII signaling...
September 27, 2017: Neuron
https://www.readbyqxmd.com/read/28950029/investigating-cyclic-nucleotide-and-cyclic-dinucleotide-binding-to-hcn-channels-by-surface-plasmon-resonance
#17
Sebastien Hayoz, Purushottam B Tiwari, Grzegorz Piszczek, Aykut Üren, Tinatin I Brelidze
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels control cardiac and neuronal rhythmicity. HCN channels contain cyclic nucleotide-binding domain (CNBD) in their C-terminal region linked to the pore-forming transmembrane segment with a C-linker. The C-linker couples the conformational changes caused by the direct binding of cyclic nucleotides to the HCN pore opening. Recently, cyclic dinucleotides were shown to antagonize the effect of cyclic nucleotides in HCN4 but not in HCN2 channels...
2017: PloS One
https://www.readbyqxmd.com/read/28928053/development-of-correction-formula-for-field-potential-duration-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-sheets
#18
Hiroko Izumi-Nakaseko, Yasunari Kanda, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Takeshi Wada, Kentaro Ando, Atsuhiko T Naito, Yuko Sekino, Atsushi Sugiyama
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD) of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28904107/hyperpolarization-activated-cyclic-nucleotide-gated-channels-potentially-modulate-axonal-excitability-at-different-thresholds
#19
Dinushi Weerasinghe, Parvathi Menon, Steve Vucic
Hyperpolarization-activated cyclic-nucleotide gated (HCN) channels mediate differences in sensory and motor axonal excitability at different thresholds in animal models. Importantly, HCN channels are responsible for voltage-gated inward rectifying (Ih) currents activated during hyperpolarization. The Ih currents exert a crucial role in determining the resting membrane potential and have been implicated in a variety of neurological disorders, including neuropathic pain. In humans, differences in biophysical properties of motor and sensory axons at different thresholds remain to be elucidated and could provide crucial pathophysiological insights in peripheral neurological diseases...
September 13, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28887304/allostery-between-two-binding-sites-in-the-ion-channel-subunit-trip8b-confers-binding-specificity-to-hcn-channels
#20
Kyle A Lyman, Ye Han, Robert J Heuermann, Xiangying Cheng, Jonathan E Kurz, Reagan E Lyman, Paul P Van Veldhoven, Dane M Chetkovich
Tetratricopeptide repeat (TPR) domains are ubiquitous structural motifs that mediate protein-protein interactions. For example, the TPR domains in the peroxisomal import receptor PEX5 enable binding to a range of type 1 peroxisomal targeting signal motifs. A homolog of PEX5, tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b), binds to and functions as an auxiliary subunit of hyperpolarization-activated cyclic nucleotide (HCN)-gated channels. Given the similarity between TRIP8b and PEX5, this difference in function raises the question of what mechanism accounts for their binding specificity...
October 27, 2017: Journal of Biological Chemistry
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