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https://www.readbyqxmd.com/read/28107393/t-cell-subset-and-stimulation-strength-dependent-modulation-of-t-cell-activation-by-kv1-3-blockers
#1
Wai-Ping Fung-Leung, Wilson Edwards, Yi Liu, Karen Ngo, Julianty Angsana, Glenda Castro, Nancy Wu, Xuejun Liu, Ronald V Swanson, Alan D Wickenden
Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1...
2017: PloS One
https://www.readbyqxmd.com/read/28105459/mog-antibody-positive-benign-unilateral-cerebral-cortical-encephalitis-with-epilepsy
#2
Ryo Ogawa, Ichiro Nakashima, Toshiyuki Takahashi, Kimihiko Kaneko, Tetsuya Akaishi, Yoshiki Takai, Douglas Kazutoshi Sato, Shuhei Nishiyama, Tatsuro Misu, Hiroshi Kuroda, Masashi Aoki, Kazuo Fujihara
OBJECTIVE: To describe the features of adult patients with benign, unilateral cerebral cortical encephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody. METHODS: In this retrospective, cross-sectional study, after we encountered an index case of MOG antibody-positive unilateral cortical encephalitis with epileptic seizure, we tested for MOG antibody using our in-house, cell-based assay in a cohort of 24 consecutive adult patients with steroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008-2014)...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#3
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105264/potential-of-renal-outer-medullary-potassium-romk-channel-as-treatments-for-hypertension-and-heart-failure
#4
EDITORIAL
Ahmed F Abdel-Magid
No abstract text is available yet for this article.
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28104983/hydrogen-sulfide-attenuates-gastric-mucosal-injury-induced-by-restraint-water-immersion-stress-via-activation-of-katp-channel-and-nf-%C3%AE%C2%BAb-dependent-pathway
#5
Hong-Zhao Sun, Shan Zheng, Kai Lu, Feng-Tian Hou, Jie-Xue Bi, Xue-Lian Liu, Shan-Shan Wang
AIM: To explore the effect of hydrogen sulfide (H2S) on restraint water-immersion stress (RWIS)-induced gastric lesions in rats and the influence of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on such an effect. METHODS: Male Wistar rats were randomly divided into a control group, a physiological saline (PS) group, a sodium hydrosulfide (NaHS) group, a glibenclamide (Gl) group, Gl plus NaHS group, a pyrrolidine dithiocarbamate (PDTC) group, and a PDTC plus NaHS group...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28104253/the-effect-of-fampridine-sr-on-cognitive-fatigue-in-a-randomized-double-blind-crossover-trial-in-patients-with-ms
#6
Sarah A Morrow, Heather Rosehart, Andrew M Johnson
BACKGROUND: Cognitive fatigue (CF) is a common complaint in persons with MS (PwMS). Fampridine-SR improves ambulation, fatigue and endurance, due to enhancing action potential formation by blocking potassium channels in demyelinated axons. Thus, through this same mechanism, it is hypothesized that Fampridine-SR could improve CF. OBJECTIVE: To determine if Fampridine-SR objectively improves CF in PwMS. METHODS: Sixty PwMS of any type with CF, defined as 3 or less correct responses when comparing the last third to the first third on the Paced Auditory Serial Addition Test (PASAT), were recruited from a tertiary care MS clinic in London (ON) Canada...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28103480/adrenergic-gate-release-for-spike-timing-dependent-synaptic-potentiation
#7
Yanling Liu, Lei Cui, Martin K Schwarz, Yan Dong, Oliver M Schlüter
Spike timing-dependent synaptic plasticity (STDP) serves as a key cellular correlate of associative learning, which is facilitated by elevated attentional and emotional states involving activation of adrenergic signaling. At cellular levels, adrenergic signaling increases dendrite excitability, but the underlying mechanisms remain elusive. Here we show that activation of β2-adrenoceptors promoted STD long-term synaptic potentiation at mouse hippocampal excitatory synapses by inactivating dendritic Kv1.1-containing potassium channels, which increased dendrite excitability and facilitated dendritic propagation of postsynaptic depolarization, potentially improving coincidental activation of pre- and postsynaptic terminals...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28103136/inhibition-of-voltage-dependent-potassium-channels-mediates-camp-potentiated-insulin-secretion-in-rat-pancreatic-%C3%AE-cells
#8
Yunfeng Liu, Xiangqin Zhong, Yaqin Ding, Lele Ren, Tao Bai, Mengmeng Liu, Zhihong Liu, Yangyan Guo, Qing Guo, Yu Zhang, Jing Yang, Yi Zhang
Insulin secretion is essential for maintenance of glucose homeostasis. An important intracellular signal regulating insulin secretion is cAMP. In this report, we showed that an increase of cAMP induced by adenylyl cyclase (AC) activator forskolin or by cAMP analog db-cAMP not only potentiated insulin secretion but also inhibited Kv channels, and these effects were reversed by AC inhibitor SQ22536. The cAMP-mediated Kv channel inhibition resulted in prolongation of action potential duration, which partly accounts for the elevation of intracellular Ca(2+) induced by activation of cAMP signaling...
January 19, 2017: Islets
https://www.readbyqxmd.com/read/28102360/modification-of-distinct-ion-channels-differentially-modulates-ca-2-dynamics-in-primary-cultured-rat-ventricular-cardiomyocytes
#9
Xichun Li, Liping Shen, Fang Zhao, Xiaohan Zou, Yuwei He, Fan Zhang, Chunlei Zhang, Boyang Yu, Zhengyu Cao
Primary cultured cardiomyocytes show spontaneous Ca(2+) oscillations (SCOs) which not only govern contractile events, but undergo derangements that promote arrhythmogenesis through Ca(2+) -dependent mechanism. We systematically examined influence on SCOs of an array of ion channel modifiers by recording intracellular Ca(2+) dynamics in rat ventricular cardiomyocytes using Ca(2+) specific fluorescence dye, Fluo-8/AM. Voltage-gated sodium channels (VGSCs) activation elongates SCO duration and reduces SCO frequency while inhibition of VGSCs decreases SCO frequency without affecting amplitude and duration...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101177/analysis-on-mechanism-of-atp-sensitive-k-channel-opener-natakalim-improving-congestive-heart-failure-after-myocardial-infarction
#10
Feng Jin
The action mechanism of natakalim, a novel ATP-sensitive potassium channel opener, was studied in ameliorating the congestive heart failure (CHF) after myocardial infarction. A total of 25 healthy Wistar male rats (age, 10 weeks; average weight, 300 g) were selected, and the CHF models after acute myocardial infarction (AMI) were prepared by ligation of left anterior descending branch. They were randomly divided into the sham operation group, the model group and the groups of 1, 3 and 9 mg/kg/day natakalims...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100740/epilepsy-associated-kcnq2-channels-regulate-multiple-intrinsic-properties-of-layer-2-3-pyramidal-neurons
#11
Zachary Niday, Virginia E Hawkins, Heun Soh, Daniel K Mulkey, Anastasios V Tzingounis
: KCNQ2 potassium channels are critical for normal brain function, as both loss-of-function and gain-of-function KCNQ2 variants can lead to various forms of neonatal epilepsy. Despite recent progress, the full spectrum of consequences as a result of KCNQ2 dysfunction in neocortical pyramidal neurons is still unknown. Here, we report that conditional ablation of Kcnq2 from mouse neocortex leads to hyperexcitability of layer 2/3 (L2/3) pyramidal neurons, exhibiting an increased input resistance and action potential frequency, as well as a reduced medium afterhyperpolarization (mAHP), a conductance partly mediated by KCNQ2 channels...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100104/theoretical-predication-of-temperature-effects-on-accommodative-processes-in-simulated-amyotrophic-lateral-sclerosis-during-hypothermia-and-hyperthermia
#12
D I Stephanova, A Kossev
Electrotonic potentials allow the accommodative processes to long-lasting subthreshold polarizing stimuli to be assessed. The present study investigates such potentials in previously simulated cases of amyotrophic lateral sclerosis, termed as ALS1, ALS2 and ALS3, respectively, when the temperature is changed during hypothermia ([Formula: see text]C) and hyperthermia ([Formula: see text]C). The ALS cases are modeled as three progressively severe uniform axonal dysfunctions along the human motor nerve fiber which is simulated by our temperature-dependent multi-layered numerical model...
January 18, 2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/28098200/cullin-7-mediates-proteasomal-and-lysosomal-degradations-of-rat-eag1-potassium-channels
#13
Po-Hao Hsu, Yu-Ting Ma, Ya-Ching Fang, Jing-Jia Huang, Yu-Ling Gan, Pei-Tzu Chang, Guey-Mei Jow, Chih-Yung Tang, Chung-Jiuan Jeng
Mammalian Eag1 (Kv10.1) potassium (K(+)) channels are widely expressed in the brain. Several mutations in the gene encoding human Eag1 K(+) channel have been associated with congenital neurodevelopmental anomalies. Currently very little is known about the molecules mediating protein synthesis and degradation of Eag1 channels. Herein we aim to ascertain the protein degradation mechanism of rat Eag1 (rEag1). We identified cullin 7 (Cul7), a member of the cullin-based E3 ubiquitin ligase family, as a novel rEag1 binding partner...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097003/application-of-a-systems-pharmacology-model-for-translational-prediction-of-herg-mediated-qtc-prolongation
#14
Verena Gotta, Zhiyi Yu, Frank Cools, Karel van Ammel, David J Gallacher, Sandra A G Visser, Frederick Sannajust, Pierre Morissette, Meindert Danhof, Piet H van der Graaf
Drug-induced QTc interval prolongation (Δ QTc) is a main surrogate for proarrhythmic risk assessment. A higher in vivo than in vitro potency for hERG-mediated QTc prolongation has been suggested. Also, in vivo between-species and patient populations' sensitivity to drug-induced QTc prolongation seems to differ. Here, a systems pharmacology model integrating preclinical in vitro (hERG binding) and in vivo (conscious dog Δ QTc) data of three hERG blockers (dofetilide, sotalol, moxifloxacin) was applied (1) to compare the operational efficacy of the three drugs in vivo and (2) to quantify dog-human differences in sensitivity to drug-induced QTc prolongation (for dofetilide only)...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28096388/competition-of-calcified-calmodulin-n-lobe-and-pip2-to-an-lqt-mutation-site-in-kv7-1-channel
#15
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/28095830/kv7-voltage-activated-potassium-channel-inhibitors-reduce-fluid-resuscitation-requirements-after-hemorrhagic-shock-in-rats
#16
Sean P Nassoiy, Kenneth L Byron, Matthias Majetschak
BACKGROUND: Recent evidence suggests that drugs targeting Kv7 channels could be used to modulate vascular function and blood pressure. Here, we studied whether Kv7 channel inhibitors can be utilized to stabilize hemodynamics and reduce resuscitation fluid requirements after hemorrhagic shock. METHODS: Anesthetized male Sprague-Dawley rats were instrumented with arterial and venous catheters for blood pressure monitoring, hemorrhage and fluid resuscitation. Series 1: Linopirdine (Kv7 channel blocker, 0...
January 17, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28094285/urinary-exosomes-contain-micrornas-capable-of-paracrine-modulation-of-tubular-transporters-in-kidney
#17
Tannia Gracia, Xiaonan Wang, Ya Su, Elizabeth E Norgett, Timothy L Williams, Pablo Moreno, Gos Micklem, Fiona E Karet Frankl
Exosomes derived from all nephron segments are present in human urine, where their functionality is incompletely understood. Most studies have focused on biomarker discovery rather than exosome function. Through sequencing we identified the miRNA repertoire of urinary exosomes from healthy volunteers; 276 mature miRNAs and 345 pre-miRNAs were identified (43%/7% of reads). Among the most abundant were members of the miR-10, miR-30 and let-7 families. Targets for the identified miRNAs were predicted using five different databases; genes encoding membrane transporters and their regulators were enriched, highlighting the possibility that these miRNAs could modulate key renal tubular functions in a paracrine manner...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094030/glucocorticoid-induced-leucine-zipper-protein-regulates-sodium-and-potassium-balance-in-the-distal-nephron
#18
Priyanka Rashmi, GianLuca Colussi, Michael Ng, Xinhao Wu, Atif Kidwai, David Pearce
Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice...
January 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28093476/muscarinic-acetylcholine-receptors-and-m-currents-underlie-efferent-mediated-slow-excitation-in-calyx-bearing-vestibular-afferents
#19
J Chris Holt, Paivi M Jordan, Anna Lysakowski, Amit Shah, Kathy Barsz, Donatella Contini
: Stimulation of vestibular efferent neurons excites calyx and dimorphic (CD) afferents. This excitation consists of fast and slow components that differ over 100-fold in activation kinetics and response duration. In turtle, efferent-mediated fast excitation arises in CD afferents when the predominant efferent neurotransmitter acetylcholine (ACh) activates calyceal nicotinic ACh receptors (nAChRs); however, it is unclear whether the accompanying efferent-mediated slow excitation is also attributed to cholinergic mechanisms...
January 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28092267/cryo-em-structure-of-the-atp-sensitive-potassium-channel-illuminates-mechanisms-of-assembly-and-gating
#20
Gregory M Martin, Craig Yoshioka, Emily A Rex, Jonathan F Fay, Qing Xie, Matthew R Whorton, James Z Chen, Show-Ling Shyng
KATP channels are metabolic sensors that couple cell energetics to membrane excitability. In pancreatic β-cells, channels formed by SUR1 and Kir6.2 regulate insulin secretion and are the targets of antidiabetic sulfonylureas. Here, we used cryo-EM to elucidate structural basis of channel assembly and gating. The structure, determined in the presence of ATP and the sulfonylurea glibenclamide, at ~6Å resolution reveals a closed Kir6.2 tetrameric core with four peripheral SUR1s each anchored to a Kir6.2 by its N-terminal transmembrane domain (TMD0)...
January 16, 2017: ELife
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