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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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/28108814/the-small-neurotoxin-apamin-blocks-not-only-small-conductance-ca-2-activated-k-channels-sk-type-but-also-the-voltage-dependent-kv1-3-channel
#8
Patrick Voos, Mehtap Yazar, René Lautenschläger, Oliver Rauh, Anna Moroni, Gerhard Thiel
Apamin is frequently used as a specific blocker of small-conductance Ca(2+)-activated (SK type) K(+) channels. Here we show that the small neurotoxin is not as specific as anticipated. It is also a high-affinity inhibitor with an IC50 of 13 nM of the Kv1.3 channel; it blocks the latter with potency similar to the Kv1.3 blocker PAP-1. Since SK type channels and Kv1.3 channels are frequently coexpressed in different tissues such as cells of the immune system, apamin must be used with caution as a pharmacological tool...
January 20, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28107393/t-cell-subset-and-stimulation-strength-dependent-modulation-of-t-cell-activation-by-kv1-3-blockers
#9
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/28094801/electronegative-ldl-mediated-cardiac-electrical-remodeling-in-a-rat-model-of-chronic-kidney-disease
#10
An-Sheng Lee, Wei-Yu Chen, Hua-Chen Chan, Ching-Hu Chung, Hsien-Yu Peng, Chia-Ming Chang, Ming-Jai Su, Chu-Huang Chen, Kuan-Cheng Chang
The mechanisms underlying chronic kidney disease (CKD)-associated higher risks for life-threatening ventricular tachyarrhythmias remain poorly understood. In rats subjected to unilateral nephrectomy (UNx), we examined cardiac electrophysiological remodeling and relevant mechanisms predisposing to ventricular arrhythmias. Adult male Sprague-Dawley rats underwent UNx (n = 6) or sham (n = 6) operations. Eight weeks later, the UNx group had higher serum blood urea nitrogen and creatinine levels and a longer electrocardiographic QTc interval than did the sham group...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087137/nos-interacting-protein-nosip-is-increased-in-the-colon-of-patients-with-hirschsprung-s-disease
#11
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
#12
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...
January 29, 2017: 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
#13
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
#14
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-hydrogen-peroxide-induced-human-arteriolar-dilation-and-its-modulation-by-coronary-artery-disease
#15
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 large-conductance Ca(2+)-activated K(+) channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) when compared with 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...
February 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/27861889/margatoxin-bound-quantum-dots-as-a-novel-inhibitor-of-the-voltage-gated-ion-channel-kv1-3
#16
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...
February 2017: 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
#17
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
#18
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
#19
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
#20
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
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