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https://www.readbyqxmd.com/read/28286469/the-ih-channel-gene-promotes-synaptic-transmission-and-coordinated-movement-in-drosophila-melanogaster
#1
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
#2
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
#3
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...
February 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28177679/reduced-expression-of-hcn-channels-in-sinoatrial-node-of-streptozotocin-induced-diabetic-rats
#4
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 risk of arrhythmias. However, knowledge of electrical remodeling in 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...
December 23, 2016: 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
#5
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...
February 7, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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/27942887/predictions-of-the-contribution-of-hcn-half-maximal-activation-potential-heterogeneity-to-variability-in-intrinsic-adaptation-of-spiral-ganglion-neurons
#14
Jason Boulet, Ian C Bruce
Spiral ganglion neurons (SGNs) exhibit a wide range in their strength of intrinsic adaptation on a timescale of 10s to 100s of milliseconds in response to electrical stimulation from a cochlear implant (CI). The purpose of this study was to determine how much of that variability could be caused by the heterogeneity in half-maximal activation potentials of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, which are known to produce intrinsic adaptation. In this study, a computational membrane model of cat type I SGN was developed based on the Hodgkin-Huxley model plus HCN and low-threshold potassium (KLT) conductances in which the half-maximal activation potential of the HCN channel was varied and the response of the SGN to pulse train and paired-pulse stimulation was simulated...
April 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/27930653/characterisation-of-development-and-electrophysiological-mechanisms-underlying-rhythmicity-of-the-avian-lymph-heart
#15
Sajjida Jaffer, Petr Valasek, Graham Luke, Munirah Batarfi, Benjamin Jason Whalley, Ketan Patel
Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart...
2016: PloS One
https://www.readbyqxmd.com/read/27911380/method-for-identifying-small-molecule-inhibitors-of-the-protein-protein-interaction-between-hcn1-and-trip8b
#16
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
#17
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...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27813693/loss-of-hcn-channel-mediated-ih-current-following-seizures-accounts-for-movement-dysfunction
#18
Jeffery A Boychuk, G Campbell Teskey
No abstract text is available yet for this article.
November 4, 2016: Channels
https://www.readbyqxmd.com/read/27807172/nitric-oxide-modulates-hcn-channels-in-magnocellular-neurons-of-the-supraoptic-nucleus-of-rats-by-an-s-nitrosylation-dependent-mechanism
#19
Melina Pires da Silva, Davi José de Almeida Moraes, André de Souza Mecawi, José Antunes Rodrigues, Wamberto Antonio Varanda
The control of the excitability in magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus has been attributed mainly to synaptic inputs from circunventricular organs. However, nitric oxide (NO), a gaseous messenger produced in this nucleus during isotonic and short-term hypertonic conditions, is an example of a modulator that can act directly on MNCs to modulate their firing rate. NO inhibits the electrical excitability of MNCs, leading to a decrease in the release of vasopressin and oxytocin. Although the effects of NO on MNCs are well established, the mechanism by which this gas produces its effect is, so far, unknown...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#20
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
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