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https://www.readbyqxmd.com/read/28467171/down-regulation-of-t-type-cav3-2-channels-by-hyperpolarization-activated-cyclic-nucleotide-gated-channel-1-hcn1-evidence-of-a-signaling-complex
#1
Jing Fan, Maria A Gandini, Fang-Xiong Zhang, Lina Chen, Ivana A Souza, Gerald W Zamponi
Formation of complexes between ion channels is important for signal processing in the brain. Here we investigate the biochemical and biophysical interactions between HCN1 channels and Cav3.2 T-type channels. We found that HCN1 co-immunoprecipitated with Cav3.2 from lysates of either mouse brain or tsA-201 cells, with the HCN1 N-terminus associating with the Cav3.2 N-terminus. Cav3.2 channel activity appeared to be functionally regulated by HCN1. The expression of HCN1 induced a decrease in Cav3.2 Ba(2+) influx (IBa(2+)) along with altered channel kinetics and a depolarizing shift in activation gating...
May 3, 2017: Channels
https://www.readbyqxmd.com/read/28455536/cation-and-voltage-dependence-of-lidocaine-inhibition-of-the-hyperpolarization-activated-cyclic-nucleotide-gated-hcn1-channel
#2
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
#3
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
#4
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/28363781/hyperpolarization-activated-current-ih-in-mouse-trigeminal-sensory-neurons-in-a-transgenic-mouse-model-of-familial-hemiplegic-migraine-type-1
#5
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/28205043/a-polygenic-risk-score-for-breast-cancer-risk-in-a-taiwanese-population
#6
Yi-Chen Hsieh, Shih-Hsin Tu, Chien-Tien Su, Er-Chieh Cho, Chih-Hsiung Wu, Mao-Chih Hsieh, Shiyng-Yu Lin, Yun-Ru Liu, Chin-Sheng Hung, Hung-Yi Chiou
BACKGROUND: Multiple common variants identified by genome-wide association studies showed limited evidence of the risk of breast cancer in Taiwan. In this study, we analyzed the breast cancer risk in relation to 13 individual single-nucleotide polymorphisms (SNPs) identified by a GWAS in an Asian population. METHODS: In total, 446 breast cancer patients and 514 healthy controls were recruited for this case-control study. In addition, we developed a polygenic risk score (PRS) including those variants significantly associated with breast cancer risk, and also evaluated the contribution of PRS and clinical risk factors to breast cancer using receiver operating characteristic curve (AUC)...
February 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28178648/polymorphisms-of-esr1-ugt1a1-hcn1-map3k1-and-cyp2b6-are-associated-with-the-prognosis-of-hormone-receptor-positive-early-breast-cancer
#7
Sung-Hsin Kuo, Shi-Yi Yang, San-Lin You, Huang-Chun Lien, Ching-Hung Lin, Po-Han Lin, Chiun-Sheng Huang
In this study, we investigated whether single nucleotide polymorphisms (SNPs) identified by genome-wide association study (GWAS) (MAP3K1, FGFR2, TNRC9, HCN1, and 5p12), and SNPs involved in the metabolism of estrogen (CYP19, COMT, ESR1, and UGT1A1), tamoxifen (CYP2C9, CYP2C19, CYP3A5, and CYP2D6), and chemotherapeutic agents (ABCB1, ALDH3A1, and CYP2B6) are associated with the prognoses of 414 hormone receptor (HR)-positive early breast cancers with negative or 1 to 3 nodal metastases. At a median follow-up period of 10...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177679/reduced-expression-of-hcn-channels-in-the-sinoatrial-node-of-streptozotocin-induced-diabetic-rats
#8
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/28131828/ep3-activation-facilitates-bladder-excitability-via-hcn-channels-on-iccs
#9
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/28088409/genome-wide-association-analysis-and-pathways-enrichment-for-lactation-persistency-in-canadian-holstein-cattle
#10
D N Do, N Bissonnette, P Lacasse, F Miglior, M Sargolzaei, X Zhao, E M Ibeagha-Awemu
Lactation persistency (LP), defined as the rate of declining milk yield after milk peak, is an economically important trait for dairy cattle. Improving LP is considered a good alternative method for increasing overall milk production because it does not cause the negative energy balance and other health issues that cows experience during peak milk production. However, little is known about the biology of LP. A genome-wide association study (GWAS) and pathway enrichment were used to explore the genetic mechanisms underlying LP...
March 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28071723/hcn1-channels-reduce-the-rate-of-exocytosis-from-a-subset-of-cortical-synaptic-terminals
#11
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
#12
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...
June 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
#13
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
#14
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
#15
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
#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/27896979/genome-wide-interaction-with-selected-type-2-diabetes-loci-reveals-novel-loci-for-type-2-diabetes-in-african-americans
#18
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
#19
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
#20
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...
May 2017: Journal of Cellular Physiology
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