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https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#1
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/28391996/molecular-mechanisms-underlying-pimaric-acid-induced-modulation-of-voltage-gated-k-channels
#2
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...
March 8, 2017: Journal of Pharmacological Sciences
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
#3
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/28270595/differential-responses-of-rabbit-ventricular-and-atrial-transient-outward-current-ito-to-the-ito-modulator-ns5806
#4
Hongwei Cheng, Mark B Cannell, Jules C Hancox
Transient outward potassium current (Ito) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of Ito may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine Ito This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular Ito Whole cell patch-clamp recordings of Ito and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes...
March 2017: Physiological Reports
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/28094801/electronegative-ldl-mediated-cardiac-electrical-remodeling-in-a-rat-model-of-chronic-kidney-disease
#6
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
#7
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/28054303/amino-acid-properties-of-trafficking-determinants-in-the-outer-pore-forming-region-of-kv1-potassium-channels-in-cell-lines
#8
Barbara Gomez, Jing Zhu, Esperanza Recio-Pinto, William B Thornhill
Different classes of Kv1 potassium channels have different trafficking patterns despite having very similar amino acid sequences. Two amino acids responsible for these differences have been identified in the outer pore turret region of Kv1.1 and Kv1.4. Here we tested a series of substitutions at these two determinants on Kv1.4. All P506 substitutions tested resulted in a significant decrease in surface protein, total protein, and protein half-life, indicating that proline is required at 506 to stabilize protein conformation and increase trafficking to the cell surface...
March 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28011270/h2s-inhibits-angiotensin-ii-induced-atrial-kv1-5-upregulation-by-attenuating-nox4-mediated-ros-generation-during-atrial-fibrillation
#9
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/27958660/angiotensin-ii-reduces-the-surface-abundance-of-kv-1-5-channels-in-arterial-myocytes-to-stimulate-vasoconstriction
#10
Michael W Kidd, Simon Bulley, Jonathan H Jaggar
KEY POINTS: Several different voltage-dependent K(+) (KV ) channel isoforms are expressed in arterial smooth muscle cells (myocytes). Vasoconstrictors inhibit KV currents, but the isoform selectivity and mechanisms involved are unclear. We show that angiotensin II (Ang II), a vasoconstrictor, stimulates degradation of KV 1.5, but not KV 2.1, channels through a protein kinase C- and lysosome-dependent mechanism, reducing abundance at the surface of mesenteric artery myocytes. The Ang II-induced decrease in cell surface KV 1...
March 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27916464/subtype-specific-block-of-voltage-gated-k-channels-by-%C3%AE-conopeptides
#11
Enrico Leipold, Florian Ullrich, Markus Thiele, Alesia A Tietze, Heinrich Terlau, Diana Imhof, Stefan H Heinemann
The neurotoxic cone snail peptide μ-GIIIA specifically blocks skeletal muscle voltage-gated sodium (NaV1.4) channels. The related conopeptides μ-PIIIA and μ-SIIIA, however, exhibit a wider activity spectrum by also inhibiting the neuronal NaV channels NaV1.2 and NaV1.7. Here we demonstrate that those μ-conopeptides with a broader target range also antagonize select subtypes of voltage-gated potassium channels of the KV1 family: μ-PIIIA and μ-SIIIA inhibited KV1.1 and KV1.6 channels in the nanomolar range, while being inactive on subtypes KV1...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mitogen-activated-kinase-kinase-7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#12
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Ruiping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical proarrhythmic side effects, culminating in a greater risk of sudden death. METHODS: We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harboring mitogen-activated kinase kinase-7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human-induced pluripotent stem cell-derived cardiomyocytes...
February 14, 2017: Circulation
https://www.readbyqxmd.com/read/27872215/intramolecular-interactions-that-control-voltage-sensitivity-in-the-jshak1-potassium-channel-from-polyorchis-penicillatus
#13
Nazlee Sharmin, Warren J Gallin
Voltage-gated potassium ion (Kv) channel proteins respond to changes in membrane potential by changing the probability of K(+) flux through an ion-selective pore. Kv channels from different paralogous and orthologous families have widely varying V50 values. The voltage-sensing transmembrane helices (S4) of different channels contain 4-7 basic residues that are responsible for transducing changes in transmembrane potential into the energy required to shift the equilibrium between the open- and closed-channel conformations...
November 21, 2016: Journal of Experimental Biology
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
#14
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/27816768/human-immunodeficiency-virus-protein-tat-induces-oligodendrocyte-injury-by-enhancing-outward-k-current-conducted-by-kv1-3
#15
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/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
#16
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/27760355/extracellular-linkers-completely-transplant-the-voltage-dependence-from-kv1-2-ion-channels-to-kv2-1
#17
Fredrik Elinder, Michael Madeja, Hugo Zeberg, Peter Århem
The transmembrane voltage needed to open different voltage-gated K (Kv) channels differs by up to 50 mV from each other. In this study we test the hypothesis that the channels' voltage dependences to a large extent are set by charged amino-acid residues of the extracellular linkers of the Kv channels, which electrostatically affect the charged amino-acid residues of the voltage sensor S4. Extracellular cations shift the conductance-versus-voltage curve, G(V), by interfering with these extracellular charges...
October 18, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27742566/atrial-fibrillation-therapeutic-potential-of-atrial-k-channel-blockers
#18
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/27731805/effects-of-ginseng-spikenard-heart-nourishing-capsule-on-inactivation-of-c-type-kv1-4-potassium-channel
#19
Zhi-Quan Wang, Xue-Jun Jiang, Guang-Yu Zhang, Ming Chen, Chuan-Feng Tong, Dong Zhang
This research is to explore the effects of traditional Chinese medicine Ginseng-spikenard heart-nourishing capsule on the inactivation of c-type Kv1.4 channels (Kv1.4∆N) in Xenopus laevis oocytes with two-electrode voltageclamp technique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4δN channels. During recording, oocytes were continuously perfused with ND96 solution (control group) and solution prepared from Ginseng-spikenard heart-nourishing capsule (experimental group)...
September 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27696527/differential-kv1-3-kca3-1-and-kir2-1-expression-in-classically-and-alternatively-activated-microglia
#20
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
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