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https://www.readbyqxmd.com/read/28782641/nitric-oxide-cgmp-signaling-via-guanylyl-cyclase-isoform-1-modulates-glutamate-and-gaba-release-in-somatosensory-cortex-of-mice
#1
Qi Wang, Evanthia Mergia, Doris Koesling, Thomas Mittmann
In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input-output curves of evoked signals, which indicated the reduction of glutamate and GABA release in NO-GC1 KO mice...
August 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28768741/theta-frequency-selectivity-in-the-somatic-spike-triggered-average-of-rat-hippocampal-pyramidal-neurons-is-dependent-on-hcn-channels
#2
Anindita Das, Rishikesh Narayanan
The ability to distill specific frequencies from complex spatiotemporal patterns of afferent inputs is a pivotal functional requirement for neurons residing in networks receiving frequency-multiplexed inputs. Although the expression of theta-frequency subthreshold resonance is established in hippocampal pyramidal neurons, it is not known if their spike initiation dynamics manifest spectral selectivity or if their intrinsic properties are tuned to process gamma-frequency inputs. Here, we measured the spike-triggered average (STA) of rat hippocampal pyramidal neurons through electrophysiological recordings and quantified spectral selectivity in their spike initiation dynamics and their coincidence detection window (CDW)...
August 2, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28762726/intracellular-uncaging-of-cgmp-with-blue-light
#3
Hitesh K Agarwal, Shenyu Zhai, D James Surmeier, Graham C R Ellis-Davies
We have made a new caged cGMP that is photolyzed with blue light. Using our recently developed derivative of 7-diethylaminocourmarin (DEAC) called DEAC450, we synthesized coumarin phosphoester derivatives of cGMP with two negative charges appended to the DEAC450 moiety. DEAC450-cGMP is freely soluble in physiological buffer without the need for any organic cosolvents. With a photolysis quantum yield of 0.18 and an extinction coefficient of 43 000 M(-1) cm(-1) at 453 nm, DEAC450-cGMP is the most photosensitive caged cGMP made to date...
August 1, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28746826/electrophysiological-properties-of-neurons-and-synapses-in-the-lateral-habenular-complex-lhb
#4
REVIEW
Franziska Wagner, Torsten Weiss, Rüdiger W Veh
Animal including human behavior is highly sophisticated. Besides reflective actions it is largely based on the desire for magnificent internal feelings, which are provided by the reward system. Its counterpart an "anti-reward" system is mainly composed of the lateral habenular complex (LHb) and its extensive interconnections with the monoaminergic cell groups in the mid- and hindbrain. The present review focuses on the neuronal composition and the internal signaling in the LHb. Morphologically six distinct types of neurons (spherical, fusiform-1, fusiform-2, polymorphic, vertical, neurogliaform) can be identified...
July 23, 2017: Pharmacology, Biochemistry, and Behavior
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
#5
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/28690143/the-brain-penetrant-5-ht7-receptor-agonist-lp-211-reduces-the-sensory-and-affective-components-of-neuropathic-pain
#6
Mirko Santello, Alberto Bisco, Natalie Elisabeth Nevian, Enza Lacivita, Marcello Leopoldo, Thomas Nevian
Neuropathic pain is a debilitating pathological condition of high clinical relevance. Changes in neuronal excitability in the anterior cingulate cortex (ACC) play a central role in the negative emotional and affective aspects of chronic pain. We evaluated the effects of LP-211, a new serotonin-receptor-type-7 (5-HT7R) agonist that crosses the blood-brain barrier, on ACC neurons in a mouse model of neuropathic pain. LP-211 reduced synaptic integration in layer 5 pyramidal neurons, which was enhanced in neuropathic pain due to a dysfunction of dendritic hyperpolarization-activated-and-cyclic-nucleotide-regulated (HCN) channels...
July 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28685234/prostanoid-ep3-receptor-agonist-sulprostone-enhances-pacemaker-activity-of-colonic-interstitial-cells-of-cajal
#7
Man Woo Kim, Han Yi Jiao, Seok Won Kim, Chan Guk Park, Mei Jin Wu, Chansik Hong, Seok Choi, Jae Yeoul Jun
EP receptor activation by PGE2 regulates gastrointestinal motility by modulating smooth muscle contractility. Interstitial cells of Cajal (ICCs) are pacemaker cells that regulate smooth muscle activity. We aimed to determine effects of the EP3 receptor agonist sulprostone on pacemaker potentials in colonic ICCs. We performed a whole cell patch clamp, RT-PCR, and Ca(2+) imaging in cultured ICCs from mouse colon. Sulprostone depolarized the membrane and increased pacemaker frequency. EP3 receptor antagonist blocked these sulprostone-induced effects...
July 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28673721/contribution-of-presynaptic-hcn-channels-to-excitatory-inputs-of-spinal-substantia-gelatinosa-neurons
#8
S-C Peng, J Wu, D-Y Zhang, C-Y Jiang, C-N Xie, T Liu
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pathological pain-associated voltage-gated ion channels. They are widely expressed in central nervous system including spinal lamina II (also named the substantia gelatinosa, SG). Here, we examined the distribution of HCN channels in glutamatergic synaptic terminals as well as their role in the modulation of synaptic transmission in SG neurons from SD rats and glutamic acid decarboxylase-67 (GAD67)-GFP mice. We found that the expression of the HCN channel isoforms was varied in SG...
July 1, 2017: Neuroscience
https://www.readbyqxmd.com/read/28667054/analysis-of-decreases-in-systemic-arterial-pressure-and-heart-rate-in-response-to-the-hydrogen-sulfide-donor-sodium-sulfide
#9
Kevin W Swan, Bryant Minkyu Song, Allen L Chen, Travis J Chen, Ryan A Chan, Bradley T Guidry, Prasad V G Katakam, Edmund K Kerut, Thomas D Giles, Philip Kadowitz
The actions of hydrogen sulfide (H2S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H2S are unclear in the anesthetized rat. The objective of the current study is to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous (iv) administration of the H2S donor sodium sulfide (Na2S) in the anesthetized Sprague-Dawley (SD) rat decreased MAP and HR and produced changes in respiratory function...
June 30, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28659282/experience-dependent-plasticity-in-accessory-olfactory-bulb-interneurons-following-male-male-social-interaction
#10
Hillary L Cansler, Marina A Maksimova, Julian P Meeks
Chemosensory information processing in the mouse accessory olfactory system guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC-interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28569901/rates-and-equilibrium-constants-of-the-ligand-induced-conformational-transition-of-an-hcn-ion-channel-protein-domain-determined-by-deer-spectroscopy
#11
Alberto Collauto, Hannah A DeBerg, Royi Kaufmann, William N Zagotta, Stefan Stoll, Daniella Goldfarb
Ligand binding can induce significant conformational changes in proteins. The mechanism of this process couples equilibria associated with the ligand binding event and the conformational change. Here we show that by combining the application of W-band double electron-electron resonance (DEER) spectroscopy with microfluidic rapid freeze quench (μRFQ) it is possible to resolve these processes and obtain both equilibrium constants and reaction rates. We studied the conformational transition of the nitroxide labeled, isolated carboxy-terminal cyclic-nucleotide binding domain (CNBD) of the HCN2 ion channel upon binding of the ligand 3',5'-cyclic adenosine monophosphate (cAMP)...
June 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28560710/hcn-channel-targets-for-novel-antidepressant-treatment
#12
REVIEW
Stacy M Ku, Ming-Hu Han
Major depressive disorder (MDD) is a chronic and potentially life threatening illness that carries a staggering global burden. Characterized by depressed mood, MDD is often difficult to diagnose and treat owing to heterogeneity of syndrome and complex etiology. Contemporary antidepressant treatments are based on improved monoamine-based formulations from serendipitous discoveries made > 60 years ago. Novel antidepressant treatments are necessary, as roughly half of patients using available antidepressants do not see long-term remission of depressive symptoms...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28469560/hcn-channel-modulation-of-synaptic-integration-in-gabaergic-interneurons-in-malformed-rat-neocortex
#13
Asher J Albertson, Andrew S Bohannon, John J Hablitz
Cortical malformations are often associated with pharmaco-resistant epilepsy. Alterations in hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN) channels have been shown to contribute to malformation associated hyperexcitability. We have recently demonstrated that expression of HCN channels and Ih current amplitudes are reduced in layer (L) 5 pyramidal neurons of rats with freeze lesion induced malformations. These changes were associated with an increased EPSP temporal summation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28458102/ivabradine-attenuates-the-anticonvulsant-potency-of-lamotrigine-but-not-that-of-lacosamide-pregabalin-and-topiramate-in-the-tonic-clonic-seizure-model-in-mice
#14
Katarzyna M Sawicka, Katarzyna Załuska, Agnieszka Wawryniuk, Karolina Załuska-Patel, Michał Szczyrek, Bartłomiej Drop, Jadwiga Daniluk, Monika Szpringer, Dorota Żółkowska, Jarogniew J Łuszczki
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are involved not only in synaptic transmission and neuronal excitability under physiological conditions, but also in seizure activity. To determine the influence of ivabradine (an HCN channel inhibitor) on the anticonvulsant potency of four novel antiepileptic drugs (AEDs: lacosamide, lamotrigine, pregabalin and topiramate) in the mouse maximal electroshock-induced seizure (MES) model. Adult male albino Swiss mice were challenged with maximal electroconvulsions (electric current of 25mA delivered via auricular electrodes)...
July 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28455536/cation-and-voltage-dependence-of-lidocaine-inhibition-of-the-hyperpolarization-activated-cyclic-nucleotide-gated-hcn1-channel
#15
Igor Putrenko, Raymond Yip, Stephan K W Schwarz, Eric A Accili
Lidocaine is known to inhibit the hyperpolarization-activated mixed cation current (Ih) in cardiac myocytes and neurons, as well in cells transfected with cloned Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels. However, the molecular mechanism of Ih inhibition by this drug has been limitedly explored. Here, we show that inhibition of Ih by lidocaine, recorded from Chinese hamster ovary (CHO) cells expressing the HCN1 channel, reached a steady state within one minute and was reversible. Lidocaine inhibition of Ih was greater at less negative voltages and smaller current amplitudes whereas the voltage-dependence of Ih activation was unchanged...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428632/cyclophosphamide-induced-hcn1-channel-upregulation-in-interstitial-cajal-like-cells-leads-to-bladder-hyperactivity-in-mice
#16
Qian Liu, Zhou Long, Xingyou Dong, Teng Zhang, Jiang Zhao, Bishao Sun, Jingzhen Zhu, Jia Li, Qingqing Wang, Zhenxing Yang, Xiaoyan Hu, Longkun Li
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28416809/perisomatic-changes-in-h-channels-regulate-depressive-behaviors-following-chronic-unpredictable-stress
#17
C S Kim, D H Brager, D Johnston
Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of HCN1 protein expression and reduction of functional Ih produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known. We found that perisomatic HCN1 protein expression and Ih-sensitive physiological measurements were significantly increased in dorsal but not in ventral CA1 region/neurons following chronic unpredictable stress (CUS), a widely accepted model for major depressive disorder...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28396445/cryoem-structure-of-a-prokaryotic-cyclic-nucleotide-gated-ion-channel
#18
Zachary M James, Andrew J Borst, Yoni Haitin, Brandon Frenz, Frank DiMaio, William N Zagotta, David Veesler
Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. These channels are characterized by the presence of a carboxyl-terminal cyclic nucleotide-binding domain (CNBD) that connects to the channel pore via a C-linker domain. Although cyclic nucleotide binding has been shown to promote CNG and HCN channel opening, the precise mechanism underlying gating remains poorly understood...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28363781/hyperpolarization-activated-current-ih-in-mouse-trigeminal-sensory-neurons-in-a-transgenic-mouse-model-of-familial-hemiplegic-migraine-type-1
#19
Francesca Eroli, Sandra Vilotti, Arn M J M van den Maagdenberg, Andrea Nistri
Transgenic knock-in (KI) mice that express CaV2.1 channels containing an R192Q gain-of-function mutation in the α1A subunit known to cause familial hemiplegic migraine type-1 in patients, exhibit key disease characteristics and provide a useful tool to investigate pathophysiological mechanisms of pain transduction. Previously, KI trigeminal sensory neurons were shown to exhibit constitutive hyperexcitability due to up-regulation of ATP-gated P2X3 receptors that trigger spike activity at a more negative threshold...
March 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28286469/the-ih-channel-gene-promotes-synaptic-transmission-and-coordinated-movement-in-drosophila-melanogaster
#20
Andrew P Hegle, C Andrew Frank, Anthony Berndt, Markus Klose, Douglas W Allan, Eric A Accili
Hyperpolarization-activated cyclic nucleotide-gated "HCN" channels, which underlie the hyperpolarization-activated current (Ih), have been proposed to play diverse roles in neurons. The presynaptic HCN channel is thought to both promote and inhibit neurotransmitter release from synapses, depending upon its interactions with other presynaptic ion channels. In larvae of Drosophila melanogaster, inhibition of the presynaptic HCN channel by the drug ZD7288 reduces the enhancement of neurotransmitter release at motor terminals by serotonin but this drug has no effect on basal neurotransmitter release, implying that the channel does not contribute to firing under basal conditions...
2017: Frontiers in Molecular Neuroscience
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