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https://www.readbyqxmd.com/read/28071723/hcn1-channels-reduce-the-rate-of-exocytosis-from-a-subset-of-cortical-synaptic-terminals
#1
Zhuo Huang, Gengyu Li, Carolina Aguado, Rafael Lujan, Mala M Shah
The hyperpolarization-activated cyclic nucleotide-gated (HCN1) channels are predominantly located in pyramidal cell dendrites within the cortex. Recent evidence suggests these channels also exist pre-synaptically in a subset of synaptic terminals within the mature entorhinal cortex (EC). Inhibition of pre-synaptic HCN channels enhances miniature excitatory post-synaptic currents (mEPSCs) onto EC layer III pyramidal neurons, suggesting that these channels decrease the release of the neurotransmitter, glutamate...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28050647/deleting-the-hcn1-subunit-of-hyperpolarization-activated-ion-channels-in-mice-impairs-acoustic-startle-reflexes-gap-detection-and-spatial-localization
#2
James R Ison, Paul D Allen, Donata Oertel
It has been proposed that the high temporal and spatial acuities of human listeners and animals tested in the hearing laboratory depend in part on the short time constants of auditory neurons that are able to preserve or sharpen the information conveyed in the timing of firing of auditory nerve fibers. We tested this hypothesis in a series of in vivo experiments, based on previous in vitro experiments showing that neuronal time constants are raised in brainstem slices when HCN1 channels are blocked or in slices obtained from Hcn1 (-/-) null mutant mice...
January 3, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/27979911/atrioventricular-node-dysfunction-and-ion-channel-transcriptome-in-pulmonary-hypertension
#3
Ian P Temple, Sunil Jit R J Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T Yamanushi, Vaikom S Mahadevan, Alison M Gurney, Ed White, Henggui Zhang, George Hart, Mark R Boyett, Halina Dobrzynski
BACKGROUND: Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node. METHODS AND RESULTS: The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node...
December 2016: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/27965425/essential-roles-of-ampa-receptor-glua1-phosphorylation-and-presynaptic-hcn-channels-in-fast-acting-antidepressant-responses-of-ketamine
#4
Ke Zhang, Ting Xu, Zhongmin Yuan, Zhisheng Wei, Vitor Nagai Yamaki, Mingfa Huang, Richard L Huganir, Xiang Cai
Although the molecular mechanism is not clear, the clinically tested drug ketamine has rapid antidepressant action that does not require the multiple weeks of treatment needed for other antidepressant drugs to have an effect. We showed that ketamine potentiated Schaffer collateral-CA1 cell excitatory synaptic transmission in hippocampal slice preparations from rodents and enhanced the phosphorylation of the GluA1 subunit on Ser(845) of the AMPA-type glutamate receptor in the hippocampal area CA1. These effects persisted when γ-aminobutyric acid (GABA) receptors were pharmacologically blocked...
December 13, 2016: Science Signaling
https://www.readbyqxmd.com/read/27922120/regulation-of-human-cardiac-potassium-channels-by-full-length-kcne3-and-kcne4
#5
Geoffrey W Abbott
Voltage-gated potassium (Kv) channels comprise pore-forming α subunits and a multiplicity of regulatory proteins, including the cardiac-expressed and cardiac arrhythmia-linked transmembrane KCNE subunits. After recently uncovering novel, N-terminally extended (L) KCNE3 and KCNE4 isoforms and detecting their transcripts in human atrium, reported here are their functional effects on human cardiac Kv channel α subunits expressed in Xenopus laevis oocytes. As previously reported for short isoforms KCNE3S and KCNE4S, KCNE3L inhibited hERG; KCNE4L inhibited Kv1...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27911380/method-for-identifying-small-molecule-inhibitors-of-the-protein-protein-interaction-between-hcn1-and-trip8b
#6
Ye Han, Kyle A Lyman, Matt Clutter, Gary E Schiltz, Quratul-Ain Ismail, Xiangying Cheng, Chi-Hao Luan, Dane M Chetkovich
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed ubiquitously throughout the brain, where they function to regulate the excitability of neurons. The subcellular distribution of these channels in pyramidal neurons of hippocampal area CA1 is regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit. Genetic knockout of HCN pore forming subunits or TRIP8b, both lead to an increase in antidepressant-like behavior, suggesting that limiting the function of HCN channels may be useful as a treatment for Major Depressive Disorder (MDD)...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27901476/the-change-of-hcn1-hcn2-mrna-expression-in-peripheral-nerve-after-chronic-constriction-injury-induced-neuropathy-followed-by-pulsed-electromagnetic-field-therapy
#7
Hui Liu, Jun Zhou, Lianbing Gu, Yunxia Zuo
Neuropathic pain is usually defined as a chronic pain state caused by peripheral or central nerve injury as a result of acute damage or systemic diseases. It remains a difficult disease to treat. Recent studies showed that the frequency of action potentials in nociceptive afferents is affected by the activity of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN) family. In the current study, we used a neuropathy rat model induced by chronic constriction injury (CCI) of sciatic nerve to evaluate the change of expression of HCN1/HCN2 mRNA in peripheral nerve and spinal cord...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896979/genome-wide-interaction-with-selected-type-2-diabetes-loci-reveals-novel-loci-for-type-2-diabetes-in-african-americans
#8
Jacob M Keaton, Jacklyn N Hellwege, Maggie C Y Ng, Nicholette D Palmer, James S Pankow, Myriam Fornage, James G Wilson, Adolfo Correa, Laura J Rasmussen-Torvik, Jerome I Rotter, Yii-DER I Chen, Kent D Taylor, Stephen S Rich, Lynne E Wagenknecht, Barry I Freedman, Donald W Bowden
Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with known T2D loci implicated in insulin secretion. To test this hypothesis, single nucleotide polymorphisms (SNPs) nominally associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, and previously associated with T2D in genome-wide association studies (GWAS) were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n=492 subjects)...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27743933/contribution-of-large-sized-primary-sensory-neuronal-sensitization-to-mechanical-allodynia-by-upregulation-of-hyperpolarization-activated-cyclic-nucleotide-gated-channels-via-cyclooxygenase-1-cascade
#9
Wei Sun, Fei Yang, Yan Wang, Han Fu, Yan Yang, Chun-Li Li, Xiao-Liang Wang, Qing Lin, Jun Chen
Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27670841/hyperexcitability-of-mesencephalic-trigeminal-neurons-and-reorganization-of-ion-channel-expression-in-a-rett-syndrome-model
#10
Max F Oginsky, Ningren Cui, Weiwei Zhong, Christopher M Johnson, Chun Jiang
People with Rett syndrome (RTT) have defects in motor function also seen in Mecp2-null mice. Motor function depends on not only central motor commands but also sensory feedback that is vulnerable to changes in excitability of propriosensory neurons. Here we report evidence for hyperexcitability of mesencephalic trigeminal (Me5) neurons in Mecp2-null mice and a novel cellular mechanism for lowering its impact. In in-vitro brain slices, the Me5 neurons in both Mecp2(-/Y) male and symptomatic Mecp2(+/-) female mice were overly excitable showing increased firing activity in comparison to their wild-type (WT) male and asymptomatic counterparts...
September 27, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27569278/expression-and-cellular-localization-of-hcn-channels-in-rat-cerebellar-granule-neurons
#11
Rafael Zúñiga, Daniela González, Claudio Valenzuela, Nelson Brown, Leandro Zúñiga
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated pore loop channels. In mammals, this family consists of four different subunits (HCN1-4) and their ion channels activity have been proposed to play an essential role in regulating the membrane potential of excitable cells. Here, we describe the expression and relative abundances of HCN channels in cerebellum and primary cultures of cerebellar granule neurons (CGN). Quantitative determination of mRNA expression levels demonstrated the existence of an accumulation pattern of transcripts in cerebellum that encode HCN2 > HCN3 = HCN4 > HCN1 subunits...
September 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27568501/hcn-channels-segregate-stimulation-evoked-movement-responses-in-neocortex-and-allow-for-coordinated-forelimb-movements-in-rodents
#12
Jeffery A Boychuk, Jordan S Farrell, Laura A Palmer, Anna C Singleton, Quentin J Pittman, G Campbell Teskey
KEY POINTS: The present study tested whether HCN channels contribute to the organization of motor cortex and to skilled motor behaviour during a forelimb reaching task. Experimental reductions in HCN channel signalling increase the representation of complex multiple forelimb movements in motor cortex as assessed by intracortical microstimulation. Global HCN1(KO) mice exhibit reduced reaching accuracy and atypical movements during a single-pellet reaching task relative to wild-type controls...
January 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27542339/inhibition-of-hcn-channel-activity-in-the-thalamus-attenuates-chronic-pain-in-rats
#13
Weihua Ding, Zerong You, Shiqian Shen, Lucy Chen, Shengmei Zhu, Jianren Mao
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the thalamus on chronic pain has not been examined. In this report, we evaluated the effect on nociceptive behaviors after infusion of a HCN channel blocker ZD7288 into the ventral posterolateral (VPL) nucleus of the thalamus in rats with neuropathic pain or monoarthritis...
September 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27496876/hyperpolarization-activated-cyclic-nucleotide-gated-channels-in-peripheral-diaphragmatic-lymphatics
#14
Daniela Negrini, Cristiana Marcozzi, Eleonora Solari, Elena Bossi, Raffaella Cinquetti, Marcella Reguzzoni, Andrea Moriondo
Diaphragmatic lymphatic function is mainly sustained by pressure changes in the tissue and serosal cavities during cardiorespiratory cycles. The most peripheral diaphragmatic lymphatics are equipped with muscle cells (LMCs), which exhibit spontaneous contraction, whose molecular machinery is still undetermined. Hypothesizing that spontaneous contraction might involve hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in lymphatic LMCs, diaphragmatic specimens, including spontaneously contracting lymphatics, were excised from 33 anesthetized rats, moved to a perfusion chamber containing HEPES-Tyrode's solution, and treated with HCN channels inhibitors cesium chloride (CsCl), ivabradine, and ZD-7288...
October 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27425615/ionic-basis-for-membrane-potential-resonance-in-neurons-of-the-inferior-olive
#15
Yoshiko Matsumoto-Makidono, Hisako Nakayama, Miwako Yamasaki, Taisuke Miyazaki, Kazuto Kobayashi, Masahiko Watanabe, Masanobu Kano, Kenji Sakimura, Kouichi Hashimoto
Some neurons have the ability to enhance output voltage to input current with a preferred frequency, which is called resonance. Resonance is thought to be a basis for membrane potential oscillation. Although ion channels responsible for resonance have been reported, the precise mechanisms by which these channels work remain poorly understood. We have found that resonance is reduced but clearly present in the inferior olivary neurons of Cav3.1 T-type voltage-dependent Ca(2+) channel knockout (KO) mice. The activation of Cav3...
July 26, 2016: Cell Reports
https://www.readbyqxmd.com/read/27371604/hyperpolarization-activated-cyclic-nucleotide-gated-channel-currents-in-neurons
#16
Mala M Shah
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage-gated ion channels that activate at potentials more negative than -50 mV and are predominantly permeable to Na(+) and K(+) ions. Four HCN subunits (HCN1-4) have been cloned. These subunits have distinct expression patterns and biophysical properties. In addition, cyclic nucleotides as well as multiple intracellular substances including various kinases and phosphatases modulate the expression and function of the subunits. Hence, the characteristics of the current, Ih, are likely to vary among neuronal subtypes...
2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27353446/patch-clamp-fluorometry-based-channel-counting-to-determine-hcn-channel-conductance
#17
Chang Liu, Changan Xie, Khade Grant, Zhuocheng Su, Weihua Gao, Qinglian Liu, Lei Zhou
Counting ion channels on cell membranes is of fundamental importance for the study of channel biophysics. Channel counting has thus far been tackled by classical approaches, such as radioactive labeling of ion channels with blockers, gating current measurements, and nonstationary noise analysis. Here, we develop a counting method based on patch-clamp fluorometry (PCF), which enables simultaneous electrical and optical recordings, and apply it to EGFP-tagged, hyperpolarization-activated and cyclic nucleotide-regulated (HCN) channels...
July 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27347074/expression-of-hyperpolarization-activated-cyclic-nucleotide-gated-channel-isoforms-in-a-canine-model-of-atrial-fibrillation
#18
Wei He, Jian Zhang, Tianyi Gan, Guojun Xu, Baopeng Tang
The aim of the present study was to analyze the mRNA and protein expression levels of atrial hyperpolarization-activated cyclic nucleotide-gated (HCN) channel isoforms in the left atrial muscle of dogs with multiple organ failure. A total of 14 beagle dogs with multiple organ failure, including seven cases with sinus rhythm and seven cases with atrial fibrillation (AF), underwent surgery to remove a sample of left atrial appendage tissue. The expression levels of a number of HCN channel subtypes were subsequently measured using quantitative polymerase chain reaction and western blot analysis...
July 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27277803/quantitative-trait-loci-and-a-novel-genetic-candidate-for-fear-learning
#19
Allison T Knoll, Lindsay R Halladay, Andrew J Holmes, Pat Levitt
UNLABELLED: Trauma- and stress-related disorders are clinically heterogeneous and associated with substantial genetic risk. Understanding the biological origins of heterogeneity of key intermediate phenotypes such as cognition and emotion can provide novel mechanistic insights into disorder pathogenesis. Performing quantitative genetics in animal models is a tractable strategy for examining both the genetic basis of intermediate phenotypes and functional testing of candidate quantitative traits genes (QTGs)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27184742/use-dependent-attenuation-of-rat-hcn1-mediated-ih-in-intact-hek293-cells
#20
Lennart Barthel, Olivia Reetz, Ulf Strauss
BACKGROUND/AIMS: Cationic currents (Ih) through the fast activating and relatively cAMP insensitive subtype of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, HCN1, are limited by cytosolic factors in mammalian cells. This cytosolic HCN1 break is boosted by changes in membrane voltage that are not characterized on a biophysical level, yet. METHODS: We overexpressed rat (r)HCN1 in human embryonic kidney cells (HEK293) and recorded pharmacologically isolated Ih in cell-attached or whole-cell mode of the patch-clamp technique...
2016: Cellular Physiology and Biochemistry
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