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https://www.readbyqxmd.com/read/28469560/hcn-channel-modulation-of-synaptic-integration-in-gabaergic-interneurons-in-malformed-rat-neocortex
#1
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
#2
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)...
April 22, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28280415/effects-of-acidic-ph-on-voltage-gated-ion-channels-in-rat-trigeminal-mesencephalic-nucleus-neurons
#9
Jin-Eon Han, Jin-Hwa Cho, In-Sun Choi, Do-Yeon Kim, Il-Sung Jang
The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K(+) and Ca(2+) channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K(+) currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K(+) currents...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28181007/regulation-of-hcn-ion-channels-by-non-canonical-cyclic-nucleotides
#10
Bryan VanSchouwen, Giuseppe Melacini
The hyperpolarization-activated cyclic-nucleotide-modulated (HCN) proteins are cAMP-regulated ion channels that play a key role in nerve impulse transmission and heart rate modulation in neuronal and cardiac cells, respectively. Although they are regulated primarily by cAMP, other cyclic nucleotides such as cGMP, cCMP, and cUMP serve as partial agonists for the HCN2 and HCN4 isoforms. By competing with cAMP for binding, these non-canonical ligands alter ion channel gating, and in turn, modulate the cAMP-dependent activation profiles...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28177679/reduced-expression-of-hcn-channels-in-the-sinoatrial-node-of-streptozotocin-induced-diabetic-rats
#11
Xin Huang, Nier Zhong, Hong Zhang, Aiqun Ma, Zuyi Yuan, Ning Guo
Diabetes mellitus (DM) is associated with an electrical remodeling of the heart, increasing the risk of arrhythmias. However, knowledge of electrical remodeling in the sinoatrial node (SAN) by DM is limited. We investigated the expression of HCN channel isoforms, HCN1-HCN4, in SAN from streptozotocin (STZ)-induced diabetic rats and the age-matched controls. We found that the STZ-induced diabetic rats have a lower intrinsic heart rate, a lengthened sinoatrial conduction time, and rate-corrected maximal sinoatrial node recovery time in vivo as well as a longer cycle length (CL) in vitro, as compared with the control...
May 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28174302/free-energy-landscape-remodeling-of-the-cardiac-pacemaker-channel-explains-the-molecular-basis-of-familial-sinus-bradycardia
#12
Stephen Boulton, Madoka Akimoto, Sam Akbarizadeh, Giuseppe Melacini
The hyperpolarization-activated and cyclic nucleotide-modulated ion channel (HCN) drives the pacemaker activity in the heart, and its malfunction can result in heart disorders. One such disorder, familial sinus bradycardia, is caused by the S672R mutation in HCN, whose electrophysiological phenotypes include a negative shift in the channel activation voltage and an accelerated HCN deactivation. The outcomes of these changes are abnormally low resting heart rates. However, the molecular mechanism underlying these electrophysiological changes is currently not fully understood...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28166960/effects-of-zd7288-a-hyperpolarization-activated-cyclic-nucleotide-gated-hcn-channel-blocker-on-term-pregnant-rat-uterine-contractility-in%C3%A2-vitro
#13
Mohammed Alotaibi, Karima Kahlat, Taoufik Nedjadi, Laiche Djouhri
The uterus is a myogenic organ that is able to produce discrete spontaneous action potentials and contractions without any stimuli. Myometrial excitability is governed by ion channels including Ca(+2) and K(+) channels, but whether or not other channels such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play an important role in regulating cellular excitability, are also involved has not been reported in uterine smooth muscles. The aim of the present study was to examine whether blocking HCN channels with a specific blocker ZD7288 would modulate the uterine contractility in a rat model...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28145004/motor-cortical-hcn-channels-a-contributor-to-coordinated-forelimb-movements-in-rodents
#14
Rune Rasmussen, Eva Meier Carlsen
No abstract text is available yet for this article.
February 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28131828/ep3-activation-facilitates-bladder-excitability-via-hcn-channels-on-iccs
#15
Chao Wu, Xingyou Dong, Qian Liu, Jingzhen Zhu, Teng Zhang, Qingqing Wang, Xiaoyang Hu, Zhenxing Yang, Longkun Li
EP3 is a receptor for prostaglandin E2 (PGE2), and although its effect on bladder excitability has attracted considerable attention, the underlying mechanism remains unclear. To investigate whether the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the interstitial cells of Cajal (ICCs) of the bladder are involved in the effect of EP3 activation on bladder excitability, wild-type mice, HCN1 knockout (HCN1(-/-)) mice and rats were used in our study. Double immunofluorescence staining and immunoprecipitation assays demonstrated the interaction between EP3 and the HCN channels...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28074902/a-reduced-mechanical-model-for-camp-modulated-gating-in-hcn-channels
#16
Stephanie Weißgraeber, Andrea Saponaro, Gerhard Thiel, Kay Hamacher
We developed an in silico mechanical model to analyze the process of cAMP-induced conformational modulations in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which conduct cations across the membrane of mammalian heart and brain cells. The structural analysis reveals a quaternary twist in the cytosolic parts of the four subunits in the channel tetramer. This motion augments the intrinsic dynamics of the very same protein structure. The pronounced differences between the cAMP bound and unbound form include a mutual interaction between the C-linker of the cyclic nucleotide binding domain (CNBD) and the linker between the S4 and S5 transmembrane domain of the channel...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28071723/hcn1-channels-reduce-the-rate-of-exocytosis-from-a-subset-of-cortical-synaptic-terminals
#17
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/28065805/genetic-perturbations-suggest-a-role-of-the-resting-potential-in-regulating-the-expression-of-the-ion-channels-of-the-kcna-and-hcn-families-in-octopus-cells-of-the-ventral-cochlear-nucleus
#18
Xiao-Jie Cao, Donata Oertel
Low-voltage-activated K(+) (gKL) and hyperpolarization-activated mixed cation conductances (gh) mediate currents, IKL and Ih, through channels of the Kv1 (KCNA) and HCN families respectively and give auditory neurons the temporal precision required for signaling information about the onset, fine structure, and time of arrival of sounds. Being partially activated at rest, gKL and gh contribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting gKL and gh also affect the coupling of somatic depolarization with the generation of action potentials...
March 2017: Hearing Research
https://www.readbyqxmd.com/read/28054154/interstitial-cell-modulation-of-pyeloureteric-peristalsis-in-the-mouse-renal-pelvis-examined-using-fibsem-tomography-and-calcium-indicators
#19
Hikaru Hashitani, Michael J Nguyen, Haruka Noda, Retsu Mitsui, Ryuhei Higashi, Keisuke Ohta, Kei-Ichiro Nakamura, Richard J Lang
Typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) and interstitial cells (ICs) within the pacemaker region of the mouse renal pelvis were examined using focused ion beam scanning electron (FIB SEM) tomography, immunohistochemistry and Ca(2+) imaging. Individual cells within 500-900 electron micrograph stacks were volume rendered and associations with their neighbours established. 'Ribbon-shaped', Ano1 Cl(-) channel immuno-reactive ICs were present in the adventitia and the sub-urothelial space adjacent to the TSMC layer...
January 4, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27965425/essential-roles-of-ampa-receptor-glua1-phosphorylation-and-presynaptic-hcn-channels-in-fast-acting-antidepressant-responses-of-ketamine
#20
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
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