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https://www.readbyqxmd.com/read/28087137/nos-interacting-protein-nosip-is-increased-in-the-colon-of-patients-with-hirschsprung-s-disease
#1
Anne-Marie O'Donnell, David Coyle, Prem Puri
PURPOSE: Voltage-dependent K(+) channels (Kv channels) participate in electrical rhythmicity and smooth muscle responses and are regulated by excitatory and inhibitory neurotransmitters. Kv channels also participate in the interstitial cell of Cajal (ICC) and smooth muscle cell (SMC) responses to neural inputs. The Kv family consists of 12 subfamilies, Kv1-Kv12, with five members of the Kv7 family identified to date: Kv7.1-Kv7.5. A recent study identified the potassium channel Kv7.5 as having a role in the excitability of ICC-IM in the mouse colon...
January 3, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28011270/h2s-inhibits-angiotensin-ii-induced-atrial-kv1-5-upregulation-by-attenuating-nox4-mediated-ros-generation-during-atrial-fibrillation
#2
Guihua Lu, Chenggui Xu, Kaiyu Tang, Juhong Zhang, Qinglang Li, Longyun Peng, Yesong Wang, Zhibin Huang, Xiuren Gao
Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study...
December 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27956907/lymphocyte-kv1-3-channels-in-the-pathogenesis-of-chronic-obstructive-pulmonary-disease-novel-therapeutic-implications-of-targeting-the-channels-by-commonly-used-drugs
#3
REVIEW
Itsuro Kazama, Tsutomu Tamada
In patients with chronic obstructive pulmonary disease (COPD), over-activated T-lymphocytes produce pro-inflammatory cytokines and proliferate in situ in the lower airways and pulmonary parenchyma, contributing substantially to the pathogenesis of the disease. Despite our understanding of the molecular mechanisms by which lymphocytes are activated, we know little about the physiological mechanisms. T-lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes and these channels play crucial roles in inducing the lymphocyte activation and proliferation...
2016: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/27922120/regulation-of-human-cardiac-potassium-channels-by-full-length-kcne3-and-kcne4
#4
Geoffrey W Abbott
Voltage-gated potassium (Kv) channels comprise pore-forming α subunits and a multiplicity of regulatory proteins, including the cardiac-expressed and cardiac arrhythmia-linked transmembrane KCNE subunits. After recently uncovering novel, N-terminally extended (L) KCNE3 and KCNE4 isoforms and detecting their transcripts in human atrium, reported here are their functional effects on human cardiac Kv channel α subunits expressed in Xenopus laevis oocytes. As previously reported for short isoforms KCNE3S and KCNE4S, KCNE3L inhibited hERG; KCNE4L inhibited Kv1...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872049/contribution-of-kv1-5-channel-to-h2o2-induced-human-arteriolar-dilation-and-its-modulation-by-coronary-artery-disease
#5
Yoshinori Nishijima, Sheng Cao, Dawid S Chabowski, Ankush Korishettar, Alyce Ge, Xiaodong Zheng, Rodney Sparapani, David D Gutterman, David X Zhang
RATIONALE: Hydrogen peroxide (H2O2) regulates vascular tone in the human microcirculation under physiological and pathophysiological conditions. It dilates arterioles by activating BKCa channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) as compared to those with CAD remain unknown. OBJECTIVE: We hypothesize that H2O2-elicited dilation involves different K(+) channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation during disease...
November 21, 2016: Circulation Research
https://www.readbyqxmd.com/read/27861889/margatoxin-bound-quantum-dots-as-a-novel-inhibitor-of-the-voltage-gated-ion-channel-kv1-3
#6
Austin B Schwartz, Anshika Kapur, Wentao Wang, Zhenbo Huang, Erminia Fardone, Goutam Palui, Hedi Mattoussi, Debra Ann Fadool
Venom-derived ion channel inhibitors have strong channel selectivity, potency, and stability; however, tracking delivery to their target can be challenging. Herein, we utilized luminescent quantum dots (QDs) conjugated to margatoxin (MgTx) as a traceable vehicle to target a voltage-dependent potassium channel, Kv1.3, which has a select distribution and well-characterized role in immunity, glucose metabolism, and sensory ability. We screened both unconjugated (MgTx) and conjugated MgTx (QD-MgTx) for their ability to inhibit Shaker channels Kv1...
November 8, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27816768/human-immunodeficiency-virus-protein-tat-induces-oligodendrocyte-injury-by-enhancing-outward-k-current-conducted-by-kv1-3
#7
Han Liu, Jianuo Liu, Enquan Xu, Guihua Tu, Minglei Guo, Shangdong Liang, Huangui Xiong
Brain white matter damage is frequently detected in patients infected with human immunodeficiency virus type 1 (HIV-1). White matter is composed of neuronal axons sheathed by oligodendrocytes (Ols), the myelin-forming cells in central nervous system. Ols are susceptible to HIV-1 viral trans-activator of transcription (Tat) and injury of Ols results in myelin sheath damage. It has been demonstrated that activation of voltage-gated K(+) (KV) channels induces cell apoptosis and Ols predominantly express K(+) channel KV1...
January 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27815390/kv1-3-channels-mark-functionally-competent-cd8-tumor-infiltrating-lymphocytes-in-head-and-neck-cancer
#8
Ameet A Chimote, Peter Hajdu, Alexandros M Sfyris, Brittany N Gleich, Trisha Wise-Draper, Keith A Casper, Laura Conforti
Tumor-infiltrating lymphocytes (TIL) are potent mediators of an antitumor response. However, their function is attenuated in solid tumors. CD8(+) T-cell effector functions, such as cytokine and granzyme production, depend on cytoplasmic Ca(2+), which is controlled by ion channels. In particular, Kv1.3 channels regulate the membrane potential and Ca(2+) influx in human effector memory T (TEM) cells. In this study, we assessed the contribution of reduced Kv1.3 and Ca(2+) flux on TIL effector function in head and neck cancer (HNC)...
January 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27802162/the-c-terminal-domain-of-kv1-3-regulates-functional-interactions-with-the-kcne4-subunit
#9
Laura Solé, Sara R Roig, Albert Vallejo-Gracia, Antonio Serrano-Albarrás, Ramón Martínez-Mármol, Michael M Tamkun, Antonio Felipe
The voltage-dependent K(+) channel Kv1.3 (also known as KCNA3), which plays crucial roles in leukocytes, physically interacts with KCNE4. This interaction inhibits the K(+) currents because the channel is retained within intracellular compartments. Thus, KCNE subunits are regulators of K(+) channels in the immune system. Although the canonical interactions of KCNE subunits with Kv7 channels are under intensive investigation, the molecular determinants governing the important Kv1.3- KCNE4 association in the immune system are unknown...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27796577/regulation-of-human-cardiac-kv1-5-channels-by-extracellular-acidification
#10
Shuang Wang, Wei-Guang Ding, Jia-Yu Bai, Futoshi Toyoda, Min-Jie Wei, Hiroshi Matsuura
Human Kv1.5 channels (hKv1.5) conduct the ultra-rapid delayed rectifier potassium current (I Kur), which plays an important role in action potential repolarization of atrial myocytes. The present study was undertaken to examine the effects of acidic pH on hKv1.5 wild-type (WT) and its pore mutant channels heterologously expressed in Chinese hamster ovary (CHO) cells using site-directed mutagenesis combined with whole-cell patch-clamp technique. Both extracellular and intracellular acidifications equally and reversely reduced the amplitude of hKv1...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27789942/comparison-of-cellular-effects-of-starch-coated-spions-and-poly-lactic-co-glycolic-acid-matrix-nanoparticles-on-human-monocytes
#11
Dominik Gonnissen, Ying Qu, Klaus Langer, Cengiz Öztürk, Yuliang Zhao, Chunying Chen, Guiscard Seebohm, Martina Düfer, Harald Fuchs, Hans-Joachim Galla, Kristina Riehemann
Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27765883/inhibitory-effects-of-telmisartan-on-culture-and-proliferation-of-and-kv1-3-potassium-channel-expression-in-peripheral-blood-cd4-t-lymphocytes-from-xinjiang-kazakh-patients-with-hypertension
#12
Sha-Sha Huang, Qiu-Bing Zhang, Qing-Yan Yuan, Si-Li He, Yuan-Ming Zhang
INTRODUCTION: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4(+) T lymphocytes derived from Xinjiang Kazakh patients with hypertension. METHODS: CD4(+) T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27742566/atrial-fibrillation-therapeutic-potential-of-atrial-k-channel-blockers
#13
REVIEW
Ursula Ravens, Katja E Odening
Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K(+)) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets...
October 12, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27696527/differential-kv1-3-kca3-1-and-kir2-1-expression-in-classically-and-alternatively-activated-microglia
#14
Hai M Nguyen, Eva M Grössinger, Makoto Horiuchi, Kyle W Davis, Lee-Way Jin, Izumi Maezawa, Heike Wulff
Microglia are highly plastic cells that can assume different phenotypes in response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) promote differentiation into classically activated M1-like microglia, which produce high levels of pro-inflammatory cytokines and nitric oxide and are thought to contribute to neurological damage in ischemic stroke and Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti-inflammatory effects and tissue repair. We here investigated whether these microglia subsets vary in their K(+) channel expression by differentiating neonatal mouse microglia into M(LPS) and M(IL-4) microglia and studying their K(+) channel expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry...
January 2017: Glia
https://www.readbyqxmd.com/read/27663736/rational-design-of-a-kv1-3-channel-blocking-antibody-as-a-selective-immunosuppressant
#15
Rongsheng E Wang, Ying Wang, Yuhan Zhang, Chase Gabrelow, Yong Zhang, Victor Chi, Qiangwei Fu, Xiaozhou Luo, Danling Wang, Sean Joseph, Kristen Johnson, Arnab K Chatterjee, Timothy M Wright, Vân T B Nguyen-Tran, John Teijaro, Argyrios N Theofilopoulos, Peter G Schultz, Feng Wang
A variable region fusion strategy was used to generate an immunosuppressive antibody based on a novel "stalk-knob" structural motif in the ultralong complementary-determining region (CDR) of a bovine antibody. The potent Kv1.3 channel inhibitory peptides Moka1-toxin and Vm24-toxin were grafted into different CDRs of the humanized antibodies BVK and Synagis (Syn) using both β-sheet and coiled-coil linkers. Structure-activity relationship efforts led to generation of the fusion protein Syn-Vm24-CDR3L, which demonstrated excellent selectivity and potency against effector human memory T cells (subnanomolar to picomolar EC50 values)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27660193/role-of-individual-disulfide-bridges-in-the-conformation-and-activity-of-spinoxin-%C3%AE-ktx6-13-a-potassium-channel-toxin-from-heterometrus-spinifer-scorpion-venom
#16
Yoko Yamaguchi, Steve Peigneur, Junyi Liu, Shiho Uemura, Takeru Nose, Selvanayagam Nirthanan, Ponnampalam Gopalakrishnakone, Jan Tytgat, Kazuki Sato
Spinoxin (SPX; α-KTx6.13), isolated from venom of the scorpion Heterometrus spinifer, is a K(+) channel-specific peptide toxin (KTx), which adopts a cysteine-stabilized α/β scaffold that is cross-linked by four disulfide bridges (Cys1-Cys5, Cys2-Cys6, Cys3-Cys7, and Cys4-Cys8). To investigate the role of the individual disulfide bonds in the structure-activity relationship of SPX, we synthesized four SPX analogs in which each pair of cysteine residues was replaced by alanine residues. The analysis of circular dichroism spectra and inhibitory activity against Kv1...
November 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27638047/comparison-of-voltage-gated-k-currents-in-arterial-myocytes-with-heterologously-expressed-k-v-subunits
#17
Robert H Cox, Samantha Fromme
We have shown that three components contribute to functional voltage gated K(+) (K v) currents in rat small mesenteric artery myocytes: (1) Kv1.2 plus Kv1.5 with Kvβ1.2 subunits, (2) Kv2.1 probably associated with Kv9.3 subunits, and (3) Kv7.4 subunits. To confirm and address subunit stoichiometry of the first two, we have compared the biophysical properties of K v currents in small mesenteric artery myocytes with those of Kv subunits heterologously expressed in HEK293 cells using whole cell voltage clamp methods...
December 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27626381/ionic-immune-suppression-within-the-tumour-microenvironment-limits-t-cell-effector-function
#18
Robert Eil, Suman K Vodnala, David Clever, Christopher A Klebanoff, Madhusudhanan Sukumar, Jenny H Pan, Douglas C Palmer, Alena Gros, Tori N Yamamoto, Shashank J Patel, Geoffrey C Guittard, Zhiya Yu, Valentina Carbonaro, Klaus Okkenhaug, David S Schrump, W Marston Linehan, Rahul Roychoudhuri, Nicholas P Restifo
Tumours progress despite being infiltrated by tumour-specific effector T cells. Tumours contain areas of cellular necrosis, which are associated with poor survival in a variety of cancers. Here, we show that necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours, causing profound suppression of T cell effector function. Elevation of the extracellular potassium concentration ([K(+)]e) impairs T cell receptor (TCR)-driven Akt-mTOR phosphorylation and effector programmes...
September 22, 2016: Nature
https://www.readbyqxmd.com/read/27573545/the-antifungal-plant-defensin-atpdf2-3-from-arabidopsis-thaliana-blocks-potassium-channels
#19
Kim Vriens, Steve Peigneur, Barbara De Coninck, Jan Tytgat, Bruno P A Cammue, Karin Thevissen
Scorpion toxins that block potassium channels and antimicrobial plant defensins share a common structural CSαβ-motif. These toxins contain a toxin signature (K-C4-X-N) in their amino acid sequence, and based on in silico analysis of 18 plant defensin sequences, we noted the presence of a toxin signature (K-C5-R-G) in the amino acid sequence of the Arabidopsis thaliana defensin AtPDF2.3. We found that recombinant (r)AtPDF2.3 blocks Kv1.2 and Kv1.6 potassium channels, akin to the interaction between scorpion toxins and potassium channels...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27571906/blockade-of-the-kv1-3-k-channel-enhances-bcg-vaccine-efficacy-by-expanding-central-memory-t-lymphocytes
#20
Dhiraj Kumar Singh, Ved Prakash Dwivedi, Anand Ranganathan, William R Bishai, Luc Van Kaer, Gobardhan Das
Tuberculosis (TB) is the oldest known infectious disease, yet there is no effective vaccine against adult pulmonary TB. Emerging evidence indicates that T helper (Th)1 and Th17 cells play important roles in host protection against TB. However, TB vaccine efficacy in mice is critically dependent on the balance between antigen-specific central memory T (Tcm) to effector memory T (Tem) cells. Specifically, a high Tcm to Tem cell ratio is essential for optimal vaccine efficacy. Here, we show that pharmacological inhibition of Kv1...
August 28, 2016: Journal of Infectious Diseases
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