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https://www.readbyqxmd.com/read/28504408/kv1-3-channels-facilitate-the-connection-between-metabolism-and-blood-flow-in-the-heart
#1
REVIEW
Vahagn Ohanyan, Liya Yin, Raffi Bardakjian, Christopher Kolz, Molly Enrick, Tatevik Hakobyan, Jordan Luli, Kathleen Graham, Mohamed Khayata, Suzanna Logan, John Kmetz, William M Chilian
The connection between metabolism and flow in the heart, metabolic dilation, is essential for cardiac function. We recently found redox-sensitive Kv1.5 channels play a role in coronary metabolic dilation; however, more than one ion channel likely plays a role in this process as animals null for these channels still showed limited coronary metabolic dilation. Accordingly, we examined the role of another Kv1 family channel, the energetically linked Kv1.3 channel, in coronary metabolic dilation. We measured myocardial blood flow (contrast echocardiography) during norepinephrine-induced increases in cardiac work (heart rate x mean arterial pressure) in WT, WT mice given correolide (preferential Kv1...
May 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28495226/a-gas-flow-model-for-layered-landfills-with-vertical-extraction-wells
#2
Shi-Jin Feng, Qi-Teng Zheng, Hai-Jian Xie
This paper developed a two-dimensional axisymmetric analytical model for layered landfills with vertical wells. The model uses a horizontal layered structure to describe the waste non-homogeneity with depth in gas generation, permeability and temperature. The governing equations in the cylindrical coordinate system were transformed to dimensionless forms and solved using a method of eigenfunction expansion. After verification, the effects of different well boundary conditions and gas extraction systems on recovery efficiency were investigated...
May 8, 2017: Waste Management
https://www.readbyqxmd.com/read/28484740/expression-of-ion-channels-in-perivascular-stem-cells-derived-from-human-umbilical-cords
#3
Eunbi Kim, Won Sun Park, Seok-Ho Hong
Potassium channels, the largest group of pore proteins, selectively regulate the flow of potassium (K(+)) ions across cell membranes. The activity and expression of K(+) channels are critical for the maintenance of normal functions in vessels and neurons, and for the regulation of cell differentiation and maturation. However, their role and expression in stem cells have been poorly understood. In this study, we isolated perivascular stem cells (PVCs) from human umbilical cords and investigated the expression patterns of big-conductance Ca(2+)-activated K(+) (BKCa) and voltage-dependent K(+) (Kv) channels using the reverse transcription polymerase chain reaction...
March 2017: Balsaeng'gwa Saengsig
https://www.readbyqxmd.com/read/28472608/epigenetic-regulation-of-voltage-gated-potassium-ion-channel-molecule-kv1-3-in-mechanisms-of-colorectal-cancer
#4
Tao He, Can Wang, Meiying Zhang, Xiaomei Zhang, Shufang Zheng, Enqiang Linghu, Mingzhou Guo
Colorectal cancer (CRC) is among the leading causes of cancer-related death throughout the world. Aberrant expression of voltage-gated potassium ion channel molecule Kv1.3 has been reported in various cancers. To explore the expression and regulation of Kv1.3 in colorectal cancer, 7 colorectal cancer cell lines and 147 cases of primary colorectal cancer were involved in this study. Kv1.3 was expressed in LOVO and SW480 cells and loss of expression was found in RKO, DLD1, SW620, HCT116, and HT29 cells. Complete methylation was found in RKO, DLD1, SW620, HCT116, and HT29 cells, partial methylation was found in LOVO and SW480 cells...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#5
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/28426823/observation-of-%C3%AF-pore-currents-in-mutant-hkv1-2_v370c-potassium-channels
#6
Pavel Tyutyaev, Stephan Grissmer
Current through the σ-pore was first detected in hKv1.3_V388C channels, where the V388C mutation in hKv1.3 channels opened a new pathway (σ-pore) behind the central α-pore. Typical for this mutant channel was inward current at potentials more negative than -100 mV when the central α-pore was closed. The α-pore blockers such as TEA+ and peptide toxins (CTX, MTX) could not reduce current through the σ-pore of hKv1.3_V388C channels. This new pathway would proceed in parallel to the α-pore in the S6-S6 interface gap...
2017: PloS One
https://www.readbyqxmd.com/read/28412597/peptide-blockers-of-kv1-3-channels-in-t-cells-as-therapeutics-for-autoimmune-disease
#7
REVIEW
K George Chandy, Raymond S Norton
The voltage-gated Kv1.3 channel in T lymphocytes is a validated therapeutic target for diverse autoimmune diseases. Here we review the discovery of Kv1.3, its physiological role in T cells, and why it is an attractive target for modulating autoimmune responses. We focus on peptide inhibitors because the first Kv1.3-selective inhibitor in human trials is a peptide derived from a marine organism. Two broad classes of peptides block Kv1.3, the first from scorpions and the second from sea anemones. We describe their structures, their binding site in the external vestibule of Kv1...
April 13, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28408885/fludarabine-inhibits-kv1-3-currents-in-human-b-lymphocytes
#8
Alicia de la Cruz, Alba Vera-Zambrano, Diego A Peraza, Carmen Valenzuela, Juan M Zapata, Gema Perez-Chacon, Teresa Gonzalez
Fludarabine (F-ara-A) is a purine analog commonly used in the treatment of indolent B cell malignancies that interferes with different aspects of DNA and RNA synthesis. KV1.3 K(+) channels are membrane proteins involved in the maintenance of K(+) homeostasis and the resting potential of the cell, thus controlling signaling events, proliferation and apoptosis in lymphocytes. Here we show that F-ara-A inhibits KV currents in human B lymphocytes. Our data indicate that KV1.3 is expressed in both BL2 and Dana B cell lines, although total KV1...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28405806/rearrangement-of-potassium-ions-and-kv1-1-kv1-2-potassium-channels-in-regenerating-axons-following-end-to-end-neurorrhaphy-ionic-images-from-tof-sims
#9
Chiung-Hui Liu, Hung-Ming Chang, Tsung-Huan Wu, Li-You Chen, Yin-Shuo Yang, To-Jung Tseng, Wen-Chieh Liao
The voltage-gated potassium channels Kv1.1 and Kv1.2 that cluster at juxtaparanodal (JXP) regions are essential in the regulation of nerve excitability and play a critical role in axonal conduction. When demyelination occurs, Kv1.1/Kv1.2 activity increases, suppressing the membrane potential nearly to the equilibrium potential of K(+), which results in an axonal conduction blockade. The recovery of K(+)-dependent communication signals and proper clustering of Kv1.1/Kv1.2 channels at JXP regions may directly reflect nerve regeneration following peripheral nerve injury...
April 12, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28399409/direct-pharmacological-targeting-of-a-mitochondrial-ion-channel-selectively-kills-tumor-cells-in%C3%A2-vivo
#10
Luigi Leanza, Matteo Romio, Katrin Anne Becker, Michele Azzolini, Livio Trentin, Antonella Managò, Elisa Venturini, Angela Zaccagnino, Andrea Mattarei, Luca Carraretto, Andrea Urbani, Stephanie Kadow, Lucia Biasutto, Veronica Martini, Filippo Severin, Roberta Peruzzo, Valentina Trimarco, Jan-Hendrik Egberts, Charlotte Hauser, Andrea Visentin, Gianpietro Semenzato, Holger Kalthoff, Mario Zoratti, Erich Gulbins, Cristina Paradisi, Ildiko Szabo
The potassium channel Kv1.3 is highly expressed in the mitochondria of various cancerous cells. Here we show that direct inhibition of Kv1.3 using two mitochondria-targeted inhibitors alters mitochondrial function and leads to reactive oxygen species (ROS)-mediated death of even chemoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28391996/molecular-mechanisms-underlying-pimaric-acid-induced-modulation-of-voltage-gated-k-channels
#11
Kazuho Sakamoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Katsuhiko Muraki, Yuji Imaizumi
Voltage-gated K(+) (KV) channels, which control firing and shape of action potentials in excitable cells, are supposed to be potential therapeutic targets in many types of diseases. Pimaric acid (PiMA) is a unique opener of large conductance Ca(2+)-activated K(+) channel. Here, we report that PiMA modulates recombinant rodent KV channel activity. The enhancement was significant at low potentials (<0 mV) but not at more positive potentials. Application of PiMA significantly shifted the voltage-activation relationships (V1/2) of rodent KV1...
April 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28389388/prolonged-immunomodulation-in-inflammatory-arthritis-using-the-selective-kv1-3-channel-blocker-hstx1-r14a-and-its-pegylated-analog
#12
Mark R Tanner, Rajeev B Tajhya, Redwan Huq, Elizabeth J Gehrmann, Kathia E Rodarte, Mustafa A Atik, Raymond S Norton, Michael W Pennington, Christine Beeton
Effector memory T lymphocytes (TEM cells) that lack expression of CCR7 are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. The Kv1.3 potassium channel is a key regulator of CCR7(-) TEM cell activation. Blocking Kv1.3 inhibits TEM cell activation and attenuates inflammation in autoimmunity, and as such, Kv1.3 has emerged as a promising target for the treatment of TEM cell-mediated autoimmune diseases. The scorpion venom-derived peptide HsTX1 and its analog HsTX1[R14A] are potent Kv1...
April 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28349975/mechanism-of-functional-interaction-between-potassium-channel-kv1-3-and-sodium-channel-navbeta1-subunit
#13
Tomoya Kubota, Ana M Correa, Francisco Bezanilla
The voltage-gated potassium channel subfamily A member 3 (Kv1.3) dominantly expresses on T cells and neurons. Recently, the interaction between Kv1.3 and NavBeta1 subunits has been explored through ionic current measurements, but the molecular mechanism has not been elucidated yet. We explored the functional interaction between Kv1.3 and NavBeta1 through gating current measurements using the Cut-open Oocyte Voltage Clamp (COVC) technique. We showed that the N-terminal 1-52 sequence of hKv1.3 disrupts the channel expression on the Xenopus oocyte membrane, suggesting a potential role as regulator of hKv1...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28300672/discovery-of-three-toxin-peptides-with-kv1-3-channel-and-il-2-cytokine-inhibiting-activities-from-non-buthidae-scorpions-chaerilus-tricostatus-and-chaerilus-tryznai
#14
Li Ding, Jing Chen, Jinbo Hao, Jiahui Zhang, Xuejun Huang, Fangfang Hu, Zheng Wu, Yaru Liu, Wenxin Li, Zhijian Cao, Yingliang Wu, Jian Li, Shan Li, Hongyan Liu, Wenlong Wu, Zongyun Chen
Non-Buthidae venomous scorpions are huge natural sources of toxin peptides; however, only a few studies have been done to understand their toxin peptides. Herein, we describe three new potential immunomodulating toxin peptides, Ctri18, Ctry68 and Ctry2908, from two non-Buthidae scorpions, Chaerilus tricostatus and Chaerilus tryznai. Sequence alignment analyses showed that Ctri18, Ctry68 and Ctry2908 are three new members of the scorpion toxin α-KTx15 subfamily. Electrophysiological experiments showed that Ctri18, Ctry68 and Ctry2908 blocked the Kv1...
March 12, 2017: Peptides
https://www.readbyqxmd.com/read/28300604/altered-activation-of-peripheral-cd8-t-cells-in-pediatric-crohn-s-disease
#15
Csaba Orbán, Dolóresz Szabó, Anna Bajnok, Barna Vásárhelyi, Tivadar Tulassay, András Arató, Gábor Veres, Gergely Toldi
AIM: Although Crohn's disease (CD) is an extensively investigated autoimmune condition, knowledge on early phase activation of lymphocytes, especially CD8+ Tc cells is scarce. Our aim was to investigate the calcium influx characteristics of CD8+ cells upon activation as well as the expression and function of Kv1.3 and IKCa1 lymphocyte potassium channels. METHODS: We took peripheral blood from 12 healthy controls, 23 CD children on conventional therapy and 6 severe CD children before and after infliximab therapy...
March 11, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28259806/awake-long-term-intranasal-insulin-treatment-does-not-affect-object-memory-odor-discrimination-or-reversal-learning-in-mice
#16
Genevieve A Bell, Debra Ann Fadool
Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm...
March 2, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28248292/potassium-channels-kv1-3-and-kca3-1-cooperatively-and-compensatorily-regulate-antigen-specific-memory-t-cell-functions
#17
Eugene Y Chiang, Tianbo Li, Surinder Jeet, Ivan Peng, Juan Zhang, Wyne P Lee, Jason DeVoss, Patrick Caplazi, Jun Chen, Søren Warming, David H Hackos, Susmith Mukund, Christopher M Koth, Jane L Grogan
Voltage-gated Kv1.3 and Ca(2+)-dependent KCa3.1 are the most prevalent K(+) channels expressed by human and rat T cells. Despite the preferential upregulation of Kv1.3 over KCa3.1 on autoantigen-experienced effector memory T cells, whether Kv1.3 is required for their induction and function is unclear. Here we show, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout (KO) rats, suggesting that KCa3...
March 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28243504/aminopyridines-for-the-treatment-of-neurologic-disorders
#18
REVIEW
Michael Strupp, Julian Teufel, Andreas Zwergal, Roman Schniepp, Kamran Khodakhah, Katharina Feil
PURPOSE OF REVIEW: To identify the different indications for the treatment of neurologic disorders with the potassium channel blockers 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP). RECENT FINDINGS: 4-AP is an effective symptomatic treatment for downbeat nystagmus (DBN), episodic ataxia type 2 (EA2) (5-10 mg TID), and impaired gait in multiple sclerosis (MS) (10 mg BID). 3,4-DAP (5 mg/d-20 mg TID) improves symptoms in Lambert-Eaton myasthenic syndrome (LEMS) (randomized placebo-controlled trials for all 4 entities)...
February 2017: Neurology. Clinical Practice
https://www.readbyqxmd.com/read/28186199/ubiquitination-mediates-kv1-3-endocytosis-as-a-mechanism-for-protein-kinase-c-dependent-modulation
#19
Ramón Martínez-Mármol, Katarzyna Styrczewska, Mireia Pérez-Verdaguer, Albert Vallejo-Gracia, Núria Comes, Alexander Sorkin, Antonio Felipe
The voltage-dependent potassium channel Kv1.3 plays essential physiological functions in the immune system. Kv1.3, regulating the membrane potential, facilitates downstream Ca(2+) -dependent pathways and becomes concentrated in specific membrane microdomains that serve as signaling platforms. Increased and/or delocalized expression of the channel is observed at the onset of several autoimmune diseases. In this work, we show that adenosine (ADO), which is a potent endogenous modulator, stimulates PKC, thereby causing immunosuppression...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179135/c-terminal-residues-in-small-potassium-channel-blockers-odk1-and-osk3-from-scorpion-venom-fine-tune-the-selectivity
#20
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
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