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voltage gated potassium channel

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https://www.readbyqxmd.com/read/28220076/actions-and-mechanisms-of-polyunsaturated-fatty-acids-on-voltage-gated-ion-channels
#1
REVIEW
Fredrik Elinder, Sara I Liin
Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28219421/regulation-of-voltage-gated-potassium-channels-attenuates-resistance-of-side-population-cells-to-gefitinib-in-the-human-lung-cancer-cell-line-nci-h460
#2
Seon Young Choi, Hang-Rae Kim, Pan Dong Ryu, So Yeong Lee
BACKGROUND: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. METHODS: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux...
February 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28216637/mutations-underlying-episodic-ataxia-type-1-antagonize-kv1-1-rna-editing
#3
Elizabeth A Ferrick-Kiddie, Joshua J C Rosenthal, Gregory D Ayers, Ronald B Emeson
Adenosine-to-inosine RNA editing in transcripts encoding the voltage-gated potassium channel Kv1.1 converts an isoleucine to valine codon for amino acid 400, speeding channel recovery from inactivation. Numerous Kv1.1 mutations have been associated with the human disorder Episodic Ataxia Type-1 (EA1), characterized by stress-induced ataxia, myokymia, and increased prevalence of seizures. Three EA1 mutations, V404I, I407M, and V408A, are located within the RNA duplex structure required for RNA editing. Each mutation decreased RNA editing both in vitro and using an in vivo mouse model bearing the V408A allele...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212804/potassium-channels-in-regulation-of-vascular-smooth-muscle-contraction-and-growth
#4
W F Jackson
Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca(2+) channels (VGCC), Ca(2+) influx through VGCC, intracellular Ca(2+), and VSM contraction. Membrane potential also affects release of Ca(2+) from internal stores and the Ca(2+) sensitivity of the contractile machinery such that K(+) channels participate in all aspects of regulation of VSM contraction...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28211063/gating-energetics-of-a-voltage-dependent-k-channel-pore-domain
#5
Greg Starek, J Alfredo Freites, Simon Bernèche, Douglas J Tobias
We used targeted molecular dynamics, informed by experimentally determined inter-atomic distances defining the pore region of open and closed states of the KvAP voltage-gated potassium channel, to generate a gating pathway of the pore domain in the absence of the voltage-sensing domains. We then performed umbrella sampling simulations along this pathway to calculate a potential of mean force that describes the free energy landscape connecting the closed and open conformations of the pore domain. The resulting energetic landscape displays three minima, corresponding to stable open, closed, and intermediate conformations with roughly similar stabilities...
February 16, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/28202576/differential-effect-of-brief-electrical-stimulation-on-voltage-gated-potassium-channels
#6
Morven Alison Cameron, Amr Al Abed, Yossi Buskila, Socrates Dokos, Nigel H Lovell, John W Morley
Electrical stimulation of neuronal tissue is a promising strategy to treat a variety of neurological disorders. The mechanism of neuronal activation by external electrical stimulation is governed by voltage-gated ion channels. This stimulus, typically brief in nature, leads to membrane potential depolarization, which increases ion flow across the membrane by increasing the open probability of these voltage-gated channels. In spiking neurons, it is activation of voltage-gated sodium channels (NaV-channels) that leads to action potential generation...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28192090/optogenetic-control-of-ca-2-and-voltage-dependent-large-conductance-bk-potassium-channels
#7
Thomas Mager, Phillip G Wood, Ernst Bamberg
Ca(2+) concentration jumps for the activation of Ca(2+) dependent ion channels or transporters can be obtained either by fast solution exchange or the use of caged Ca(2+). Here we report on an alternate optogenetic method for activation of Ca(2+) and voltage dependent large conductance (BK) potassium channels. This was achieved through the use of the light-gated Ca(2+) permeable Channelrhodopsin 2 variant, CatCh, with enhanced Ca(2+) permeability, which produces locally [Ca(2+)] in the μM range on the inner side of the membrane, without significant [Ca(2+)] increase in the cytosol...
February 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28188958/potassium-channel-gene-associations-with-joint-processing-speed-and-white-matter-impairments-in-schizophrenia
#8
Heather A Bruce, Peter Kochunov, Sara A Paciga, Craig L Hyde, Xing Chen, Zhiyong Xie, Baohong Zhang, Hualin S Xi, Patricio O'Donnell, Christopher Whelan, Christian R Schubert, Alfredo Bellon, Seth A Ament, Dinesh K Shukla, Xiaoming Du, Laura M Rowland, Hugh O'Neill, L Elliot Hong
Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons...
February 11, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28182562/in-silico-modeling-of-the-functional-role-of-reduced-sialylation-in-sodium-and-potassium-channel-gating-of-mouse-ventricular-myocytes
#9
Dongping Du, Hui Yang, Andrew R Ednie, Eric S Bennett
Cardiac ion channels are highly glycosylated membrane proteins, with up to 30% of the protein's mass containing glycans. Heart diseases often accompany individuals with congenital disorders of glycosylation (CDG). However, cardiac dysfunction among CDG patients is not yet fully understood. There is an urgent need to study how aberrant glycosylation impacts cardiac electrical signaling. Our previous works reported that congenitally reduced sialylation achieved through deletion of the sialyltransferase gene, ST3Gal4, leads to altered gating of voltage-gated Na+ and K+ channels (Nav and Kv, respectively)...
February 6, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28179135/c-terminal-residues-in-small-potassium-channel-blockers-odk1-and-osk3-from-scorpion-venom-fine-tune-the-selectivity
#10
Alexey I Kuzmenkov, Steve Peigneur, Anton O Chugunov, Valentin M Tabakmakher, Roman G Efremov, Jan Tytgat, Eugene V Grishin, Alexander A Vassilevski
We report isolation, sequencing, and electrophysiological characterization of OSK3 (α-KTx 8.8 in Kalium and Uniprot databases), a potassium channel blocker from the scorpion Orthochirus scrobiculosus venom. Using the voltage clamp technique, OSK3 was tested on a wide panel of 11 voltage-gated potassium channels expressed in Xenopus oocytes, and was found to potently inhibit Kv1.2 and Kv1.3 with IC50 values of ~331nM and ~503nM, respectively. OdK1 produced by the scorpion Odontobuthus doriae differs by just two C-terminal residues from OSK3, but shows marked preference to Kv1...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28166327/neurological-autoantibody-prevalence-in-epilepsy-of-unknown-etiology
#11
Divyanshu Dubey, Abdulradha Alqallaf, Ryan Hays, Matthew Freeman, Kevin Chen, Kan Ding, Mark Agostini, Steven Vernino
Importance: Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy. Objective: To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology. Design, Setting, and Participants: Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified...
February 6, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28150887/differential-effects-of-energy-deprivation-on-intracellular-sodium-homeostasis-in-neurons-and-astrocytes
#12
REVIEW
Niklas J Gerkau, Cordula Rakers, Gabor C Petzold, Christine R Rose
The maintenance of a low intracellular sodium concentration by the Na(+) /K(+) -ATPase (NKA) is critical for brain function. In both neurons and glial cells, NKA activity is required to counteract changes in the sodium gradient due to opening of voltage- and ligand-gated channels and/or activation of sodium-dependent secondary active transporters. Because NKA consumes about 50% of cellular ATP, sodium homeostasis is strictly dependent on an intact cellular energy metabolism. Despite the high energetic costs of electrical signaling, neurons do not contain significant energy stores themselves, but rely on a close metabolic interaction with surrounding astrocytes...
February 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28122815/the-intrinsically-liganded-cyclic-nucleotide-binding-homology-domain-promotes-kcnh-channel-activation
#13
Yaxian Zhao, Marcel P Goldschen-Ohm, João H Morais-Cabral, Baron Chanda, Gail A Robertson
Channels in the ether-à-go-go or KCNH family of potassium channels are characterized by a conserved, C-terminal domain with homology to cyclic nucleotide-binding homology domains (CNBhDs). Instead of cyclic nucleotides, two amino acid residues, Y699 and L701, occupy the binding pocket, forming an "intrinsic ligand." The role of the CNBhD in KCNH channel gating is still unclear, however, and a detailed characterization of the intrinsic ligand is lacking. In this study, we show that mutating both Y699 and L701 to alanine, serine, aspartate, or glycine impairs human EAG1 channel function...
February 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28115470/intracellular-and-non-neuronal-targets-of-voltage-gated-potassium-channel-complex-antibodies
#14
Bethan Lang, Mateusz Makuch, Teresa Moloney, Inga Dettmann, Swantje Mindorf, Christian Probst, Winfried Stoecker, Camilla Buckley, Charles R Newton, M Isabel Leite, Paul Maddison, Lars Komorowski, Jane Adcock, Angela Vincent, Patrick Waters, Sarosh R Irani
OBJECTIVES: Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined...
January 23, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28109880/dynamics-of-the-eag1-k-channel-selectivity-filter-assessed-by-molecular-dynamics-simulations
#15
Harald Bernsteiner, Michael Bründl, Anna Stary-Weinzinger
EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4...
January 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28107393/t-cell-subset-and-stimulation-strength-dependent-modulation-of-t-cell-activation-by-kv1-3-blockers
#16
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
#17
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/28102360/modification-of-distinct-ion-channels-differentially-modulates-ca-2-dynamics-in-primary-cultured-rat-ventricular-cardiomyocytes
#18
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/28096388/competition-of-calcified-calmodulin-n-lobe-and-pip2-to-an-lqt-mutation-site-in-kv7-1-channel
#19
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 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28090678/the-epileptic-and-nonepileptic-spectrum-of-paroxysmal-dyskinesias-channelopathies-synaptopathies-and-transportopathies
#20
REVIEW
Roberto Erro, Kailash P Bhatia, Alberto J Espay, Pasquale Striano
Historically, the syndrome of primary paroxysmal dyskinesias was considered a group of disorders as a result of ion channel dysfunction. This proposition was primarily based on the discovery of mutations in ion channels, which caused other episodic neurological disorders such as epilepsy and migraine and also supported by the frequent association between paroxysmal dyskinesias and epilepsy. However, the discovery of the genes responsible for the 3 classic forms of paroxysmal dyskinesias disproved this ion channel theory...
January 16, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
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