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https://www.readbyqxmd.com/read/28445150/modulation-of-the-inwardly-rectifying-potassium-channel-kir4-1-by-the-pro-invasive-mir-5096-in-glioblastoma-cells
#1
Dominique Thuringer, Gaetan Chanteloup, Jonathan Boucher, Nicolas Pernet, Christophe Boudesco, Gaetan Jego, Aurelien Chatelier, Patrick Bois, Jessica Gobbo, Laurent Cronier, Eric Solary, Carmen Garrido
Inwardly rectifying potassium channels (Kir), and especially the barium-sensitive Kir4.1 encoded by KCNJ10, are key regulators of glial functions. A lower expression or mislocation of Kir4.1 is detected in human brain tumors. MicroRNAs participate in the regulation of ionic channels and associated neurologic disorders. Here, we analyze effects of miR-5096 on the Kir4.1 expression and function in two glioblastoma cell lines, U87 and U251. Using whole-cell patch-clamp and western-blot analysis, we show that cell loading with miR-5096 decreases the Kir4...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444637/phase-dependent-astroglial-alterations-in-li-pilocarpine-induced-status-epilepticus-in-young-rats
#2
Adriana Fernanda K Vizuete, Matheus Mittmann Hennemann, Carlos Alberto Gonçalves, Diogo Losch de Oliveira
Epilepsy prevalence is high in infancy and in the elderly population. Lithium-pilocarpine is widely used to induce experimental animal models of epilepsy, leading to similar neurochemical and morphological alterations to those observed in temporal lobe epilepsy. As astrocytes have been implicated in epileptic disorders, we hypothesized that specific astroglial changes accompany and contribute to epileptogenesis. Herein, we evaluated time-dependent astroglial alterations in the hippocampus of young (27-day-old) rats at 1, 14 and 56 days after Li-pilocarpine-induced status epilepticus (SE), corresponding to different phases in this model of epilepsy...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28443815/molecular-mechanism-of-voltage-dependent-potentiation-of-kcnh-potassium-channels
#3
William N Zagotta, Gucan Dai
EAG-like (ELK) voltage-gated potassium channels are abundantly expressed in the brain. These channels exhibit a behavior called voltage-dependent potentiation (VDP), which appears to be a specialization to dampen the hyperexitability of neurons. VDP manifests as a potentiation of current amplitude, hyperpolarizing shift in voltage sensitivity, and slowing of deactivation in response to a depolarizing prepulse. Here we show that VDP of D. rerio ELK channels involves the structural interaction between the intracellular N-terminal eag domain and C-terminal CNBHD...
April 26, 2017: ELife
https://www.readbyqxmd.com/read/28443635/expression-and-localisation-of-two-pore-domain-k2p-background-leak-potassium-ion-channels-in-the-mouse-retina
#4
Steven Hughes, Russell G Foster, Stuart N Peirson, Mark W Hankins
Two-pore domain (K2P) potassium channels perform essential roles in neuronal function. These channels produce background leak type potassium currents that act to regulate resting membrane potential and levels of cellular excitability. 15 different K2P channels have been identified in mammals and these channels perform important roles in a wide number of physiological systems. However, to date there is only limited data available concerning the expression and role of K2P channels in the retina. In this study we conduct the first comprehensive study of K2P channel expression in the retina...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442953/role-of-flupirtine-in-reducing-preoperative-anxiety-of-patients-undergoing-craniotomy-procedure
#5
Ghanshyam Yadav, Gaurav Jain, Malkhan Singh
BACKGROUND: Kv7 neuronal channels are recognized as a potential drug target for anxiolytic effects. We hypothesize that flupirtine as a potassium channel opener would effectively reduce the preoperative anxiety of patients undergoing craniotomy procedure. METHODS: In prospective-double-blinded fashion, 124 counseled patients were randomized to receive 5 sequential doses of capsule flupirtine 100 mg (F Group) or physically similar starch capsules (C Group), at 12 h intervals during preoperative hospitalization...
April 2017: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#6
P Richard Grimm, Richard Coleman, Eric Delpire, Paul A Welling
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK)...
April 25, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28442472/functional-and-metabolomic-consequences-of-atp-dependent-potassium-channel-inactivation-in-human-islets
#7
Changhong Li, Amanda M Ackermann, Kara E Boodhansingh, Tricia R Bhatti, Chengyang Liu, Jonathan Schug, Nicolai Doliba, Bing Han, Karen E Cosgrove, Indraneel Banerjee, Franz M Matschinsky, Itzhak Nissim, Klaus H Kaestner, Ali Naji, N Scott Adzick, Mark J Dunne, Charles A Stanley, Diva D De León
Loss-of-function mutations of β-cell KATP channels cause the most severe form of congenital hyperinsulinism (KATPHI). KATPHI is characterized by fasting and protein-induced hypoglycemia that is unresponsive to medical therapy. For a better understanding of the pathophysiology of KATPHI, we examined cytosolic calcium, insulin secretion, oxygen consumption, and [U-(13)C]glucose metabolism in islets isolated from the pancreases of children with KATPHI who required pancreatectomy. Basal cytosolic calcium ([Ca(2+)] i ) and insulin secretion were higher in KATPHI islets compared to controls...
April 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28438792/reconstitution-of-abscisic-acid-signaling-from-the-receptor-to-dna-via-bhlh-transcription-factors
#8
Yohei Takahashi, Yuta Ebisu, Ken-Ichiro Shimazaki
The plant hormone abscisic acid (ABA) confers drought tolerance in plants through stomatal closure and regulation of gene expression. The complex consisting of the ABA receptor PYRABACTIN RESISTANCE/REGULATORY COMPONENTS OF ABA RECEPTOR (PYR/RCAR), type 2C protein phosphatase (PP2C), and SNF1-related protein kinase 2 (SnRK2) has a key role in ABA signaling. Basic helix-loop-helix (bHLH) transcriptional activator ABA-RESPONSIVE KINASE SUBSTRATE1 (AKS1, also known as FBH3), is released from DNA by phosphorylation-induced monomerization in response to ABA in guard cells...
April 24, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28435971/-mechanisms-underlying-rat-coronary-arterial-vasoconstriction-induced-by-blockade-of-inward-rectifier-potassium-channels-with-bacl2
#9
Fang-Wen Fan, Ze-Fang He, Meng Shi, Rong Yang, Xiao-Min Hou, Yu Liu, Ming-Sheng Zhang
In order to explore the mechanisms underlying the vasoconstriction induced by blockade of inward rectifier K(+) channels (Kir) with BaCl2, myogenic tone of isolated rat coronary artery (RCA) was recorded with wire myograph. The dependence of BaCl2- induced contraction on intracellular Ca(2+) ([Ca(2+)]i) release and extracellular Ca(2+) ([Ca(2+)]o) influx was studied by Ca(2+) deprivation and restoration. The mechanisms underlying BaCl2-induced RCA contraction were investigated with specific inhibitors. BaCl2 (0...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28434841/transcriptional-dependencies-in-diffuse-intrinsic-pontine-glioma
#10
Surya Nagaraja, Nicholas A Vitanza, Pamelyn J Woo, Kathryn R Taylor, Fang Liu, Lei Zhang, Meng Li, Wei Meng, Anitha Ponnuswami, Wenchao Sun, Jie Ma, Esther Hulleman, Tomek Swigut, Joanna Wysocka, Yujie Tang, Michelle Monje
Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade...
April 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28433656/impaired-endothelium-derived-hyperpolarization-type-relaxation-in-superior-mesenteric-arteries-isolated-from-female-otsuka-long-evans-tokushima-fatty-rats
#11
Takayuki Matsumoto, Shota Kobayashi, Makoto Ando, Shun Watanabe, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433559/the-kcnh2-ivs9-28a-g-mutation-causes-aberrant-isoform-expression-and-herg-trafficking-defect-in-cardiomyocytes-derived-from-patients-affected-by-long-qt-syndrome-type-2
#12
Manuela Mura, Ashish Mehta, Chrishan J Ramachandra, Rita Zappatore, Federica Pisano, Maria Chiara Ciuffreda, Vincenzo Barbaccia, Lia Crotti, Peter J Schwartz, Winston Shim, Massimiliano Gnecchi
BACKGROUND: Long QT Syndrome type 2 (LQT2) is caused by mutations in the KCNH2 gene that encodes for the α-subunit (hERG) of the ion channel conducting the rapid delayed rectifier potassium current (IKr). We have previously identified a disease causing mutation (IVS9-28A/G) in the branch point of the splicing of KCNH2 intron 9. However, the mechanism through which this mutation causes the disease is unknown. METHODS AND RESULTS: We generated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from fibroblasts of two IVS9-28A/G mutation carriers...
April 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28432473/vasopressin-and-vasopressin-antagonists-in-heart-failure
#13
Julie K Vishram-Nielsen, Finn Gustafsson
Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels of arginine vasopressin (AVP), a peptide hormone produced in the hypothalamus, play a role in development of hyponatremia, and AVP and its surrogate, copeptin, are related to changes in osmolality, hemodynamics, neuro-hormones as well as in overall outcome in HF patients...
April 22, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#14
Richard Desplantes, Christian Lévêque, Benjamin Muller, Manuela Lotierzo, Géraldine Ferracci, Michel Popoff, Michael Seagar, Robert Mamoun, Oussama El Far
The development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432047/delayed-lgi1-seropositivity-in-voltage-gated-potassium-channel-vgkc-complex-antibody-limbic-encephalitis
#15
Michael Sweeney, Jonathan Galli, Scott McNally, Anne Tebo, Thomas Haven, Perla Thulin, Stacey L Clardy
We utilise a clinical case to highlight why exclusion of voltage-gated potassium channel (VGKC)-complex autoantibody testing in serological evaluation of patients may delay or miss the diagnosis. A 68-year-old man presented with increasing involuntary movements consistent with faciobrachial dystonic seizures (FBDS). Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) seronegativity. Aggressive immunotherapy with methylprednisolone and plasmapheresis was started early in the course of his presentation...
April 20, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28431970/effects-of-natural-and-synthetic-isothiocyanate-based-h2s-releasers-against-chemotherapy-induced-neuropathic-pain-role-of-kv7-potassium-channels
#16
Lorenzo Di Cesare Mannelli, Elena Lucarini, Laura Micheli, Ilaria Mosca, Paolo Ambrosino, Maria Virginia Soldovieri, Alma Martelli, Lara Testai, Maurizio Taglialatela, Vincenzo Calderone, Carla Ghelardini
Hydrogen sulfide (H2S) is a crucial signaling molecule involved in several physiological and pathological processes. Nonetheless, the role of this gasotransmitter in the pathogenesis and treatment of neuropathic pain is controversial. The aim of the present study was to investigate the pain relieving profile of a series of slow releasing H2S donors (the natural allyl-isothiocyanate and the synthetics phenyl- and carboxyphenyl-isothiocyanate) in animal models of neuropathic pain induced by paclitaxel or oxaliplatin, anticancer drugs characterized by a dose-limiting neurotoxicity...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431776/gliclazide
#17
Fatmah A M Al-Omary
Gliclazide is a second-generation oral hypoglycemic drug used for the treatment of noninsulin-dependent diabetes mellitus. It belongs to the sulfonylurea class that stimulates insulin secretion from pancreatic β-cells by inhibiting ATP-dependent potassium channels. Gliclazide also possesses unique antioxidant properties and other beneficial hemobiological effects. This profile represents a comprehensive description of the physical properties, chemical synthesis, spectroscopic characterization (FTIR, (1)H NMR, (13)C NMR, UV, and single-crystal X-ray), methods of analysis, pharmacological actions, and pharmacokinetic and pharmacodynamic properties of the title drug...
2017: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/28431243/cryo-em-structure-of-the-open-human-ether-%C3%A3-go-go-related-k-channel-herg
#18
Weiwei Wang, Roderick MacKinnon
The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have determined the molecular structure of hERG to 3.8 Å using cryo-electron microscopy. In this structure, the voltage sensors adopt a depolarized conformation, and the pore is open. The central cavity has an atypically small central volume surrounded by four deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#19
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#20
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
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