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https://www.readbyqxmd.com/read/29650696/npy-induces-stress-resilience-via-down-regulation-of-i-h-in-principal-neurons-of-rat-basolateral-amygdala
#1
Heika Silveira Villarroel, Maria Bompolaki, James Mackay, Ana Pamela Miranda Tapia, Sheldon D Michaelson, Randy J Leitermann, Robert A Marr, Janice H Urban, William F Colmers
Neuropeptide Y (NPY) expression is tightly linked with the development of stress resilience in rodents and humans. Local NPY injections targeting the basolateral amygdala (BLA) produce long-term behavioral stress resilience in male rats via an unknown mechanism. Previously, we showed that activation of NPY Y1 receptors hyperpolarizes BLA principal neurons (PNs) through inhibition of the hyperpolarization-activated, depolarizing H-current, Ih The present studies tested whether NPY treatment induces stress resilience by modulating Ih NPY (10 pmol) was delivered daily for 5 days bilaterally into the BLA to induce resilience; thereafter the electrophysiological properties of PNs and the expression of Ih in the BLA were characterized...
April 12, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29596995/applying-ketamine-to-alleviate-the-ptsd-like-effects-by-regulating-the-hcn1-related-bdnf
#2
Lanwei Hou, Yirui Qi, Hongwei Sun, Gang Wang, Qi Li, Yanyu Wang, Zuoji Zhang, Zhongde Du, Lin Sun
BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with concurrent anxiety and depression symptoms, and reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF) which promotes the proliferation and survival of neurons. The hyperpolarization-activated cyclic nucleotide-gated channel 1(HCN1) could be inhibited by the ketamine, a drug to alleviate depression and anxiety, and regulated the BDNF expression, however, the effects of ketamine in alleviating PTSD symptoms by regulating the HCN1-related BDNF have been poorly perceived...
March 26, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29460132/the-role-of-hcn-channels-in-peristaltic-dysfunction-in-human-ureteral-tuberculosis
#3
Fan He, Zhenxing Yang, Xingyou Dong, Zhenqiang Fang, Qian Liu, Xiaoyan Hu, Shanhong Yi, Longkun Li
OBJECTIVE: To explore the role of HCN channels in ureteral peristaltic dysfunction by comparing the changes in HCN channel levels between normal and tuberculous ureters. METHODS: A total of 32 specimens of human upper ureters were collected by nephrectomy from patients with renal tumor (control group, n = 16) or from patients with renal tuberculosis (experimental group, n = 16); the two groups did not receive radiotherapy, chemotherapy, immunotherapy, or any other special treatment before the surgical procedure...
April 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29444426/inferior-olive-hcn1-channels-coordinate-synaptic-integration-and-complex-spike-timing
#4
Derek L F Garden, Marlies Oostland, Marta Jelitai, Arianna Rinaldi, Ian Duguid, Matthew F Nolan
Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the inferior olive (IO), are critical for motor coordination, and are central to theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels expressed by IO neurons have been considered as pacemaker currents important for oscillatory and resonant dynamics. Here, we demonstrate that in vitro, network actions of HCN1 channels enable bidirectional glutamatergic synaptic responses, while local actions of HCN1 channels determine the timing and waveform of synaptically driven action potentials...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29436607/decreased-hyperpolarization-activated-cyclic-nucleotide-gated-channels-are-involved-in-bladder-dysfunction-associated-with-spinal-cord-injury
#5
Qian Liu, Chao Wu, Shengquan Huang, Qingjian Wu, Tao Zhou, Xiaobing Liu, Xin Liu, Xiaoyan Hu, Longkun Li
Spinal cord injury (SCI) leads to bereft voluntary control of bladder, but the possible role of spontaneous excited system in bladder of SCI patients is poorly understood. Hyper-polarization-activated cyclic nucleotide-gated (HCN) channels are deemed to regulate the spontaneous contraction of bladder, our study explored the functional role of HCN channels in SCI induced neurogenic bladder. Sixty female Sprague-Dawley rats were randomized into control, sham and SCI groups. Rat models subjected to SCI at S2 levels were successfully established and were assessed using hematoxylin and eosin staining and cystometry...
May 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29427087/neuroinflammation-alters-integrative-properties-of-rat-hippocampal-pyramidal-cells
#6
Federica Frigerio, Corey Flynn, Ye Han, Kyle Lyman, Joaquin N Lugo, Teresa Ravizza, Antoine Ghestem, Julika Pitsch, Albert Becker, Anne E Anderson, Annamaria Vezzani, Dane Chetkovich, Christophe Bernard
Neuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long-lasting inflammatory response in hippocampal microglia associated with a concomitant upregulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic AMP-gated channel type 1 (HCN1) protein level while Kv4...
February 9, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29396561/next-generation-sequencing-of-av-nodal-reentrant-tachycardia-patients-identifies-broad-spectrum-of-variants-in-ion-channel-genes
#7
Laura Andreasen, Gustav Ahlberg, Chuyi Tang, Charlotte Andreasen, Jacob P Hartmann, Jacob Tfelt-Hansen, Elijah R Behr, Steen Pehrson, Stig Haunsø, LuCamp, Peter E Weeke, Thomas Jespersen, Morten S Olesen, Jesper H Svendsen
Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases...
February 2, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29394509/increase-of-hyperpolarization-activated-cyclic-nucleotide-gated-current-in-the-aberrant-excitability-of-spinal-muscular-atrophy
#8
Hsing-Jung Lai, Chien-Lin Chen, Li-Kai Tsai
OBJECTIVE: The pathophysiology of spinal muscular atrophy (SMA) is still unclear. METHODS: The nerve excitability test in SMA patients and a mouse model of SMA was carried out to explore the pathophysiology of nodal and internodal currents, and quantitative PCR, western blotting, and whole-cell patch-clamp recording were used for the identified hypothesis. RESULTS: The nerve excitability test in SMA patients showed increased inward rectification in the current-threshold relationship and increased overshoot after hyperpolarizing threshold electrotonus, which indicates increased hyperpolarization-activated cyclic nucleotide-gated (HCN) current; these findings correlated with disease severity...
March 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29366880/increased-hcn-channel-activity-in-the-gasserian-ganglion-contributes-to-trigeminal-neuropathic-pain
#9
Weihua Ding, Zerong You, Shiqian Shen, Jinsheng Yang, Grewo Lim, Jason T Doheny, Shengmei Zhu, Yi Zhang, Lucy Chen, Jianren Mao
Orofacial neuropathic pain caused by trigeminal nerve injury is a debilitating condition with limited therapeutic options. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability and are involved in the development and maintenance of chronic pain. However, the effect of HCN channel activity in the Gasserian ganglion on trigeminal neuropathic pain has not been examined. We evaluated nociceptive behaviors after microinjection of the HCN channel blockers ZD7288 or ivabradine into the Gasserian ganglion in rats with trigeminal nerve injury...
January 31, 2018: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29339292/selective-hcn1-block-as-a-strategy-to-control-oxaliplatin-induced-neuropathy
#10
F Resta, L Micheli, A Laurino, V Spinelli, T Mello, L Sartiani, L Di Cesare Mannelli, E Cerbai, C Ghelardini, M N Romanelli, G Mannaioni, A Masi
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies...
March 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29335607/grid-scale-drives-the-scale-and-long-term-stability-of-place-maps
#11
Caitlin S Mallory, Kiah Hardcastle, Jason S Bant, Lisa M Giocomo
Medial entorhinal cortex (MEC) grid cells fire at regular spatial intervals and project to the hippocampus, where place cells are active in spatially restricted locations. One feature of the grid population is the increase in grid spatial scale along the dorsal-ventral MEC axis. However, the difficulty in perturbing grid scale without impacting the properties of other functionally defined MEC cell types has obscured how grid scale influences hippocampal coding and spatial memory. Here we use a targeted viral approach to knock out HCN1 channels selectively in MEC, causing the grid scale to expand while leaving other MEC spatial and velocity signals intact...
February 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29225577/-i-f-channel-as-an-emerging-therapeutic-target-for-cardiovascular-diseases-a-review-of-current-evidence-and-controversies
#12
REVIEW
Hayelom G Mengesha, Tadesse B Tafesse, Mohammed H Bule
In 2015, non-communicable diseases accounted for 39.5 million (70%) of the total 56.4 million deaths that occurred globally, of which 17.7 million (45%) were due to cardiovascular diseases. An elevated heart rate is considered to be one of the independent predictors and markers of future cardiovascular diseases. A variety of experimental and epidemiological studies have found that atherosclerosis, heart failure, coronary artery disease, stroke, and arrhythmia are linked to elevated heart rate. Although there are established drugs to reduce the heart rate, these drugs have undesirable side effects...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29047147/case-control-pharmacogenetic-study-of-hcn1-hcn2-variants-and-genetic-generalized-epilepsies
#13
Shu-Zhi Wu, Hua Ye, Xiao-Guo Yang, Zhi-Li Lu, Qiang Qu, Jian Qu
Epilepsy is a common complex neurological disorder, and some forms are resistant to drug treatment. The HCN1/HCN2 genes encode hyperpolarization-activated cyclic nucleotide-gated channels, which play important roles in the electrophysiology of neurons. We investigated the association between HCN1/HCN2 variants and drug resistance or the risk of genetic generalized epilepsies (GGEs). We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to assess nine variants of HCN1/HCN2 in 284 healthy participants and 483 GGEs (279 drug-responsive, 204 drug-resistant)...
March 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29046615/integrated-genomic-characterization-of-cancer-genes-in-glioma
#14
Aijun Liang, Bin Zhou, Wei Sun
BACKGROUND: Cancers are caused by the acquisition of somatic mutations. Numerous efforts have been made to characterize the key driver genes and pathways in glioma, however, the etiology of glioma is still not completely known. This study was implemented to characterize driver genes in glioma independently of somatic mutation frequencies. METHODS: Driver genes and pathways were predicted by OncodriveCLUST, OncodriveFM, Icages, Drgap and Dendrix in glioma using 31,958 somatic mutations from TCGA, followed by an integrative characterization of driver genes...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28989025/aav-mediated-conversion-of-human-pluripotent-stem-cell-derived-pacemaker
#15
Patrick K W Chan, Lin Geng, Yi Gao, Wendy Keung, Ronald A Li
Malfunction of nodal pacemaker (Pm) cardiomyocytes (CMs) due to diseases or aging leads to rhythm generation disorders, necessitating electronic Pm implantation. We functionally reprogrammed human pluripotent stem cell (hPSC) derived-ventricular (V) CMs into -PmCMs via recombinant adeno-associated virus serotype 9 (rAAV9)-mediated overexpression of engineered HCN1 channel (HCN1ΔΔΔ) whose S3-S4 linker has been strategically deleted by design to promote cardiac pacemaking. rAAV9-HCN1ΔΔΔ-reprogrammed hPSC-PmCMs converted from -VCMs showed automaticity and action potential parameters typical of native nodal PmCMs...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28880996/dravet-syndrome-and-its-mimics-beyond-scn1a
#16
REVIEW
Dora Steel, Joseph D Symonds, Sameer M Zuberi, Andreas Brunklaus
OBJECTIVE: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by the onset of prolonged febrile and afebrile seizures in infancy, and evolving to drug-resistant epilepsy with accompanying cognitive, behavioral, and motor impairment. Most cases are now known to be caused by pathogenic variants in the sodium channel gene SCN1A, but several other genes have also been implicated. This review examines current understanding of the role of non-SCN1A genes in DS, and what is known about phenotypic similarities and differences...
November 2017: Epilepsia
https://www.readbyqxmd.com/read/28878030/the-hyperpolarization-activated-cyclic-nucleotide-gated-channels-from-biophysics-to-pharmacology-of-a-unique-family-of-ion-channels
#17
REVIEW
Laura Sartiani, Guido Mannaioni, Alessio Masi, Maria Novella Romanelli, Elisabetta Cerbai
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important members of the voltage-gated pore loop channels family. They show unique features: they open at hyperpolarizing potential, carry a mixed Na/K current, and are regulated by cyclic nucleotides. Four different isoforms have been cloned (HCN1-4) that can assemble to form homo- or heterotetramers, characterized by different biophysical properties. These proteins are widely distributed throughout the body and involved in different physiologic processes, the most important being the generation of spontaneous electrical activity in the heart and the regulation of synaptic transmission in the brain...
October 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28871229/gabapentin-modulates-hcn4-channel-voltage-dependence
#18
Han-Shen Tae, Kelly M Smith, A Marie Phillips, Kieran A Boyle, Melody Li, Ian C Forster, Robert J Hatch, Robert Richardson, David I Hughes, Brett A Graham, Steven Petrou, Christopher A Reid
Gabapentin (GBP) is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on hyperpolarization-activated cation (HCN) channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2, and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV(+)) or calretinin positive (CR(+)) inhibitory neurons...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28855177/small-functional-i-f-current-in-sinoatrial-pacemaker-cells-of-the-brown-trout-salmo-trutta-fario-heart-despite-strong-expression-of-hcn-channel-transcripts
#19
Minna Hassinen, Jaakko Haverinen, Matti Vornanen
Funny current ( I f ), formed by hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), is supposed to be crucial for the membrane clock regulating the cardiac pacemaker mechanism. We examined the presence and activity of HCN channels in the brown trout ( Salmo trutta fario ) sinoatrial (SA) pacemaker cells and their putative role in heart rate ( f H ) regulation. Six HCN transcripts (HCN1, HCN2a, HCN2ba, HCN2bb, HCN3, and HCN4) were expressed in the brown trout heart. The total HCN transcript abundance was 4...
December 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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
#20
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...
September 3, 2017: Channels
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