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https://www.readbyqxmd.com/read/28103132/functional-gains-in-energy-and-cell-metabolism-after-tspo-gene-insertion
#1
Guo-Jun Liu, Ryan J Middleton, Winnie Wai-Ying Kam, David Y Chin, Claire R Hatty, Ronald H Y Chan, Richard B Banati
Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28102743/expression-and-alteration-of-bkca-channels-in-the-sphincter-of-oddi-s-from-rabbits-with-hypercholesterolemia
#2
Dan Feng, Haiyan Nan, Wen Wang, Linfeng Yan, Pang Du, Lin Zuo, Kun Zhang, Minggao Zhao, Guangbin Cui
This study aimed to investigate the expression and function of BKCa channels in the Sphincter of Oddi (SO) in a rabbit model of hypercholesterolemia (HC). New Zealand white rabbits were randomly divided into two groups: the control group was fed standard chow (n = 18) whereas the high-cholesterol group was fed cholesterol-enriched chow containing 1.5% cholesterol (n = 18). The serum cholesterol level was significantly greater in the HC groups than in the control group, but there was no significant difference in body weight between the control and HC groups...
January 19, 2017: Channels
https://www.readbyqxmd.com/read/28100478/adropin-acts-in-the-rat-paraventricular-nucleus-to-influence-neuronal-excitability
#3
Spencer P Loewen, Alastair V Ferguson
Adropin is a peptide hormone with cardiovascular and metabolic roles in the periphery, including effects on glucose and lipid homeostasis. Central administration of adropin has been shown to inhibit water intake in rats, however, the site at which central adropin acts has yet to be elucidated. The hypothalamic paraventricular nucleus (PVN), a critical autonomic control center, plays essential roles in the control of fluid balance, energy homeostasis and cardiovascular regulation, and is therefore a potential target for centrally acting adropin...
January 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28099880/modifications-of-inhibitory-transmission-onto-pyramidal-neurons-by-postnatal-exposure-to-mk-801-effects-of-enriched-environment
#4
Amir Shojaei, Afsaneh Kamali Anaraki, Javad Mirnajafi-Zadeh, Nafiseh Atapour
Early enriched environment (EE) prevents several deficits associated with postnatal MK-801 [N-Methyl-D-Aspartate (NMDA) receptor antagonist] treatment such as cognitive and locomotor deficits. We sought physiological correlates to such changes by looking at inhibitory synaptic inputs onto pyramidal cells in a prefrontal cortex slice preparation. Pharmacologically isolated γ-amino-butyric acid A (GABAA) receptor-mediated currents were measured using whole-cell patch clamp recordings. Wistar rats were raised in standard or EE from birth up to the time of experiments and were injected with saline or MK-801 (1mg/kg) on postnatal days (P) 6-10...
January 15, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28097492/activation-of-trpm2-and-trpv1-channels-in-dorsal-root-ganglion-by-nadph-oxidase-and-protein-kinase-c-molecular-pathways-a-patch-clamp-study
#5
Mustafa Nazıroğlu
Despite considerable research, the mechanisms of neuropathic pain induced by excessive oxidative stress production and overload calcium ion (Ca(2+)) entry in dorsal root ganglion (DRG) remain substantially unidentified. The transient receptor potential melastatin 2 (TRPM2) and vanilloid 1 (TRPV1) channels are activated with different stimuli including oxidative stress. TRPM2 and TRPV1 have been shown to be involved in induction of neuropathic pain. However, the activation mechanisms of TRPM2 and TRPV1 via NADPH oxidase and protein kinase C (PKC) pathways are poorly understood...
January 17, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28096388/competition-of-calcified-calmodulin-n-lobe-and-pip2-to-an-lqt-mutation-site-in-kv7-1-channel
#6
William Sam Tobelaim, Meidan Dvir, Guy Lebel, Meng Cui, Tal Buki, Asher Peretz, Milit Marom, Yoni Haitin, Diomedes E Logothetis, Joel Alan Hirsch, Bernard Attali
Voltage-gated potassium 7.1 (Kv7.1) channel and KCNE1 protein coassembly forms the slow potassium current IKS that repolarizes the cardiac action potential. The physiological importance of the IKS channel is underscored by the existence of mutations in human Kv7.1 and KCNE1 genes, which cause cardiac arrhythmias, such as the long-QT syndrome (LQT) and atrial fibrillation. The proximal Kv7.1 C terminus (CT) binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2), but the role of CaM in channel function is still unclear, and its possible interaction with PIP2 is unknown...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094801/electronegative-ldl-mediated-cardiac-electrical-remodeling-in-a-rat-model-of-chronic-kidney-disease
#7
An-Sheng Lee, Wei-Yu Chen, Hua-Chen Chan, Ching-Hu Chung, Hsien-Yu Peng, Chia-Ming Chang, Ming-Jai Su, Chu-Huang Chen, Kuan-Cheng Chang
The mechanisms underlying chronic kidney disease (CKD)-associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations. Eight weeks later, the UNx group had higher serum blood urea nitrogen and creatinine levels and a longer electrocardiographic QTc interval than did the sham group...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093336/peripheral-nerve-injury-potentiates-excitatory-synaptic-transmission-in-locus-coeruleus-neurons
#8
Kambiz Rohampour, Hossein Azizi, Yaghoub Fathollahi, Saeed Semnanian
Peripheral nerve injury (PNI) is believed to cause maladaptive changes at synaptic level, leading to neuropathic pain which is difficult to treat with common analgesic drugs. Noradrenergic locus coeruleus (LC) neurons have a crucial role in neuropathic pain modulation. In this study we examined whether chronic constriction injury (CCI) could affect glutamatergic synaptic transmission in LC neurons. CCI was performed on P10 to P12 Sprague Dawley pups. Seven days after CCI, horizontal slices of brainstem (300μm thick) were prepared and whole-cell patch clamp recording was performed...
January 13, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28093211/pharmacological-properties-of-sak3-a-novel-t-type-voltage-gated-ca-2-channel-enhancer
#9
Yasushi Yabuki, Kazuya Matsuo, Hisanao Izumi, Hidaka Haga, Takashi Yoshida, Minoru Wakamori, Akira Kakehi, Kenji Sakimura, Takaichi Fukuda, Kohji Fukunaga
T-type voltage-gated Ca(2+) channels (T-VGCCs) function in the pathophysiology of epilepsy, pain and sleep. However, their role in cognitive function remains unclear. We previously reported that the cognitive enhancer ST101, which stimulates T-VGCCs in rat cortical slices, was a potential Alzheimer's disease therapeutic. Here, we introduce a more potent T-VGCC enhancer, SAK3 (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'-imidazo [1,2-a]pyridin]-2-ene-3-carboxylate), and characterize its pharmacological properties in brain...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28087340/electrophysiological-alterations-in-diaphragm-muscle-caused-by-abdominal-ischemia-reperfusion
#10
Seckin Tuncer, Nizamettin Dalkilic, Ilksen Burat
Ischemia-reperfusion injury is the major complication of abdominal aortic surgery, and it mainly affects the lower extremities and remote organs. In the present study, the electrophysiological alterations in diaphragm that underlie the post-operative respiratory dysfunction were investigated. Wistar Albino rats were randomly divided into two groups: SHAM (only laparotomy was performed) and IR (abdominal aorta was clamped for 30min and reperfused for 2h). Following the operational period diaphragm muscles were isolated and electrophysiological experiments were carried out in-vitro...
January 10, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28079757/pathogenesis-of-abdominal-pain-in-bowel-obstruction-role-of-mechanical-stress-induced-upregulation-of-nerve-growth-factor-in-gut-smooth-muscle-cells
#11
You-Min Lin, Yu Fu, John Winston, Ravi Radhakrishnan, Sushil K Sarna, Li-Yen M Huang, Xuan-Zheng Shi
Abdominal pain is one of the major symptoms in bowel obstruction (BO); its cellular mechanisms remain incompletely understood. We tested the hypothesis that mechanical stress in obstruction upregulates expression of nociception mediator nerve growth factor (NGF) in gut smooth muscle cells (SMC), and NGF sensitizes primary sensory nerve to contribute to pain in BO. Partial colon obstruction was induced with a silicon band implanted in the distal bowel of Sprague-Dawley rats. Colon-projecting sensory neurons in the dorsal root ganglia (DRG, T13 to L2) were identified for patch clamp and gene expression studies...
January 6, 2017: Pain
https://www.readbyqxmd.com/read/28077540/leukemia-inhibitory-factor-lif-potentiates-antinociception-activity-and-inhibits-tolerance-induction-of-opioids
#12
H J Tu, K H Kang, S Y Ho, H C Liou, H H Liou, C P Lin, W M Fu
BACKGROUND: The efficacy of opioids typically decreases after long-term use owing to the development of tolerance. Glial activation and the upregulation of proinflammatory cytokines are related to the induction of tolerance. We investigated the effect of leukemia inhibitory factor (LIF) on morphine analgesia and tolerance. METHODS: LIF concentrations in rat spinal cords were measured by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) after morphine administration...
October 2016: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28075010/stimulatory-actions-of-a-novel-thiourea-derivative-on-large-conductance-calcium-activated-potassium-channels
#13
Sheng-Nan Wu, Jyh-Haur Chern, Santai Shen, Hwei-Hisen Chen, Ying-Ting Hsu, Chih-Chin Lee, Ming-Huan Chan, Ming-Chi Lai, Feng-Shiun Shie
AIM: In this study, we examine whether an anti-inflammatory thiourea derivative, compound #326, actions on ion channels. METHODS: The effects of compound #326 on Ca(2+) -activated K(+) channels were evaluated by patch-clamp recordings obtained in cell-attached, inside-out or whole-cell configuration. RESULTS: In pituitary GH3 cells, compound #326 increased the amplitude of Ca(2+) -activated K(+) currents (IK(Ca) ) with an EC50 value of 11...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28073887/perioperative-predictors-of-permanent-pacing-and-long-term-dependence-following-tricuspid-valve-surgery-a-multicentre-analysis
#14
Philip L Mar, Christopher R Angus, Rajesh Kabra, Christopher K Migliore, Rohan Goswami, Leah A John, Yixi Tu, Rakesh Gopinathannair
AIMS: Permanent pacemaker placement (PPM) is often required after valvular surgery and is especially common following tricuspid valve surgery [tricuspid valve repair or replacement (TVR)]. Literature suggests that surgical intervention for isolated tricuspid valve disease is becoming more prevalent. Predictors of PPM dependency following TVR are currently unknown and would be clinically useful from a prognostication standpoint. METHODS AND RESULTS: We conducted a multicentre, retrospective study to assess perioperative factors of TVR that predispose to PPM placement and long-term PPM dependency from 2008 to 2014...
January 10, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28072605/oxytocin-alleviates-orofacial-mechanical-hypersensitivity-associated-with-infraorbital-nerve-injury-via-vasopressin-1a-receptors-of-the-rat-trigeminal-ganglia
#15
Asako Kubo, Masamichi Shinoda, Ayano Katagiri, Mamoru Takeda, Tatsuro Suzuki, Junichi Asaka, David C Yeomans, Koichi Iwata
Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons, and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In the present study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin following PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG)...
January 7, 2017: Pain
https://www.readbyqxmd.com/read/28072464/genistein-and-tyrphostin-ag556-decrease-human-atrial-ultra-rapidly-activating-delayed-rectifier-potassium-current-by-inhibiting-egfr-tyrosine-kinase
#16
Guo-Sheng Xiao, Yan-Hui Zhang, Wei Wu, Hai-Ying Sun, Yan Wang, Gui-Rong Li
BACKGROUND AND PURPOSE: The ultra-rapidly activating delayed rectifier K(+) current IKur (encoded by Kv1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). EXPERIMENTAL APPROACH: Whole-cell patch voltage-clamp technique, and immunoprecipitation/western blotting analysis were used to investigate whether the PTK inhibitors genistein, Tyrphostin AG556 (AG556) and PP2 regulate human atrial IKur , and hKv1...
January 10, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28069954/quality-control-mechanisms-exclude-incorrect-polymerases-from-the-eukaryotic-replication-fork
#17
Grant D Schauer, Michael E O'Donnell
The eukaryotic genome is primarily replicated by two DNA polymerases, Pol ε and Pol δ, that function on the leading and lagging strands, respectively. Previous studies have established recruitment mechanisms whereby Cdc45-Mcm2-7-GINS (CMG) helicase binds Pol ε and tethers it to the leading strand, and PCNA (proliferating cell nuclear antigen) binds tightly to Pol δ and recruits it to the lagging strand. The current report identifies quality control mechanisms that exclude the improper polymerase from a particular strand...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069705/multilevel-analyses-of-scn5a-mutations-in-arrhythmogenic-right-ventricular-dysplasia-cardiomyopathy-suggest-non-canonical-mechanisms-for-disease-pathogenesis
#18
Anneline S J M Te Riele, Esperanza Agullo-Pascual, Cynthia A James, Alejandra Leo-Macias, Marina Cerrone, Mingliang Zhang, Xianming Lin, Bin Lin, Nara L Sobreira, Nuria Amat-Alarcon, Roos F Marsman, Brittney Murray, Crystal Tichnell, Jeroen F van der Heijden, Dennis Dooijes, Toon A B van Veen, Harikrishna Tandri, Steven J Fowler, Richard N W Hauer, Gordon Tomaselli, Maarten P van den Berg, Matthew R G Taylor, Francesca Brun, Gianfranco Sinagra, Arthur A M Wilde, Luisa Mestroni, Connie R Bezzina, Hugh Calkins, J Peter van Tintelen, Lei Bu, Mario Delmar, Daniel P Judge
AIMS: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is often associated with desmosomal mutations. Recent studies suggest an interaction between the desmosome and sodium channel protein Nav1.5. We aimed to determine the prevalence and biophysical properties of mutations in SCN5A (the gene encoding Nav1.5) in ARVD/C. METHODS AND RESULTS: We performed whole-exome sequencing in six ARVD/C patients (33% male, 38.2 ± 12.1 years) without a desmosomal mutation...
January 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28069411/age-related-alterations-of-neuronal-excitability-and-voltage-dependent-ca-2-current-in-a-spontaneous-mouse-model-of-alzheimer-s-disease
#19
Hua-Long Wang, Xiao-Hui Xian, Qiao-Yun Song, Chao Pang, Jia-Lei Wang, Ming-Wei Wang, Wen-Bin Li
Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder, characterized by a progressive dysfunction of central neurons, and senescence-accelerated mouse prone 8 (SAMP8), a spontaneous AD mouse model, appears to be an excellent model to investigate the process of AD. Previous studies have indicated that neuronal excitability is impaired in transgenic AD mice. In this study, the cognition of SAMP8 mice was tested using the passive avoidance task and Morris water maze; whole-cell current-clamp recordings were used to evaluate the neuronal excitability, including the resting membrane potential, the number of action potentials, and after-hyperpolarization; and the voltage-dependent Ca(2+) current in hippocampal slices was measured using whole-cell voltage-clamp recordings...
January 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28066143/acepromazine-inhibits-herg-potassium-ion-channels-expressed-in-human-embryonic-kidney-293-cells
#20
Young Shin Joo, Hong Joon Lee, Jin-Sung Choi, Ki-Wug Sung
The effects of acepromazine on human ether-à-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an IC50 value of 1.5 µM and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV...
January 2017: Korean Journal of Physiology & Pharmacology
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