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https://www.readbyqxmd.com/read/28924048/a-mutant-of-the-bmk-antitumor-analgesic-peptide-exhibits-reduced-inhibition-to-hnav1-4-and-hnav1-5-channels-while-retaining-analgesic-activity
#1
Yijia Xu, Xiangxue Meng, Xue Hou, Jianfang Sun, Xiaohua Kong, Yuqi Sun, Zeyu Liu, Yuanyuan Ma, Ye Niu, Yongbo Song, Yong Cui, Mingyi Zhao, Jinghai Zhang
Scorpion toxins can kill other animals by inducing paralysis and arrhythmia, which limits the potential applications of these agents in the clinical management of diseases. Antitumor-analgesic peptide (AGAP), purified from Buthus martensii Karsch (BmK), has been proved to possess analgesic and antitumor activities. Trp38, a conserved aromatic residue of AGAP, might play an important role in mediating AGAP activities according to the sequence and homology modeling analyses. Therefore, an AGAP mutant W38G was generated, and effects of both AGAP and the mutant W38G were examine by whole-cell patch clamp techniques on the sodium channels hNav1...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28919217/population-based-beat-to-beat-qt-analysis-from-holter-recordings-in-the-long-qt-syndrome
#2
Alex Page, Scott McNitt, Xiaojuan Xia, Wojciech Zareba, Jean-Philippe Couderc
The increasing dissemination of wearable ECG recorders (e.g. Holter, patches, and strap sensors) enables the acquisition of large amounts of data during long periods of time. However, the clinical value of these long-term continuous recordings is hindered by the lack of automatic tools to extract clinically relevant information (other than non-sinus and life-threatening rhythms) from such long-term data, particularly when targeting population-based research. In this work, we propose and test a new tool for analyzing beat-to-beat interval measurements and extracting features from Holter ECGs...
August 10, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28916636/electrophysiological-heterogeneity-of-pacemaker-cells-in-rabbit-intercaval-region-including-sa-node-insights-from-recording-multiple-ion-currents-in-each-cell
#3
Oliver Monfredi, Kenta Tsutsui, Bruce D Ziman, Michael D Stern, Edward G Lakatta, Victor A Maltsev
Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear, yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPC) sampled from the para-cristal, inter-caval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts...
September 15, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28913625/calcium-release-dependent-inactivation-precedes-formation-of-the-tubular-system-in-developing-rat-cardiac-myocytes
#4
Katarina Macková, Alexandra Zahradníková, Matej Hoťka, Barbora Hoffmannová, Ivan Zahradník, Alexandra Zahradníková
Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes...
September 14, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28899000/rhoa-rock-signalling-is-necessary-for-lateralization-and-differentiation-of-the-developing-sinoatrial-node
#5
Rebecca Vicente-Steijn, Tim P Kelder, Leon G Tertoolen, Lambertus J Wisse, Daniël A Pijnappels, Robert E Poelmann, Martin J Schalij, Marco C deRuiter, Adriana C Gittenberger-de Groot, Monique R M Jongbloed
Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28898995/uncovering-the-arrhythmogenic-potential-of-trpm4-activation-in-atrial-derived-hl-1-cells-using-novel-recording-and-numerical-approaches
#6
Yaopeng Hu, Yubin Duan, Ayako Takeuchi, Lin Hai-Kurahara, Jun Ichikawa, Keizo Hiraishi, Tomohiro Numata, Hiroki Ohara, Gentaro Iribe, Michio Nakaya, Masayuki X Mori, Satoshi Matsuoka, Genshan Ma, Ryuji Inoue
Aims: Transient receptor potential cation channel subfamily melastatin member 4 (TRPM4), a Ca2+-activated nonselective cation channel abundantly expressed in the heart, has been implicated in conduction block and other arrhythmic propensities associated with cardiac remodelling and injury. The present study aimed to quantitatively evaluate the arrhythmogenic potential of TRPM4. Methods and results: Patch clamp and biochemical analyses were performed using expression system and an immortalized atrial cardiomyocyte cell line (HL-1), and numerical model simulation was employed...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28895301/early-leaflet-thrombosis-complicating-transcatheter-implantation-of-a-sapien-3-valve-in-a-native-right-ventricular-outflow-tract
#7
Mounir Riahi, Philipp Blanke, John Webb, Ronald G Carere
A 59-year-old female with Tetralogy of Fallot had a previous complete repair with RVOT patch enlargement. She developed subsequent severe symptomatic (NYHA III) pulmonary regurgitation with severe RV dilatation. She had a concomitant interstitial lung disease secondary to hypersensitivity pneumonitis that precluded her from cardiac surgery. After preprocedural assessment using computed tomography, echocardiography and invasive angiography we decided to implant a 29 mm Edwards Sapien 3 valve without pre-stenting...
September 12, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28893911/molecular-and-functional-characterization-of-the-endothelial-atp-sensitive-potassium-channel
#8
Qadeer Aziz, Yiwen Li, Naomi Anderson, Leona Ojake, Elena Tsisanova, Andrew Tinker
ATP-sensitive potassium (KATP) channels are widely expressed in the cardiovascular system where they regulate a range of biological activities by linking cellular metabolism with membrane excitability. KATP channels in vascular smooth muscle have a well-defined role in regulating vascular tone. KATP channels are also thought to be expressed in vascular endothelial cells (ECs), but their presence and function in this context is less clear. As a result, we aimed to investigate the molecular composition and physiological role of endothelial KATP channels...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28888004/cardiomyocyte-coculture-on-layered-fibrous-scaffolds-assembled-from-micropatterned-electrospun-mats
#9
Yaowen Liu, Guisen Xu, Jiaojun Wei, Qiang Wu, Xiaohong Li
Challenges remain in engineering cardiac tissues with functional and morphological properties similar to those of native myocardium. In the current study, micropatterned fibrous mats are obtained by deposition of electrospun fibers on lithographic collectors to reproduce the anisotropic structure of myocardium, and carbon nanotubes are included in fibers to provide conductivities at the same level of cardiac muscles. The patterned mats are assembled layer-by-layer into patterned scaffolds for coculture of primary cardiomyocytes (CMs) with cardiac fibroblasts (CFs) and endothelial cells (ECs)...
December 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28880874/discovery-and-mode-of-action-of-a-novel-analgesic-%C3%AE-toxin-from-the-african-spider-ceratogyrus-darlingi
#10
Silmara R Sousa, Joshua S Wingerd, Andreas Brust, Christopher Bladen, Lotten Ragnarsson, Volker Herzig, Jennifer R Deuis, Sebastien Dutertre, Irina Vetter, Gerald W Zamponi, Glenn F King, Paul F Alewood, Richard J Lewis
Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi. Cd1a reversibly paralysed sheep blowflies (PD50 of 1318 pmol/g) and inhibited human Cav2.2 (IC50 2.6 μM) but not Cav1.3 or Cav3.1 (IC50 > 30 μM) in fluorimetric assays...
2017: PloS One
https://www.readbyqxmd.com/read/28878692/optimization-of-an-in-silico-cardiac-cell-model-for-proarrhythmia-risk-assessment
#11
Sara Dutta, Kelly C Chang, Kylie A Beattie, Jiansong Sheng, Phu N Tran, Wendy W Wu, Min Wu, David G Strauss, Thomas Colatsky, Zhihua Li
Drug-induced Torsade-de-Pointes (TdP) has been responsible for the withdrawal of many drugs from the market and is therefore of major concern to global regulatory agencies and the pharmaceutical industry. The Comprehensive in vitro Proarrhythmia Assay (CiPA) was proposed to improve prediction of TdP risk, using in silico models and in vitro multi-channel pharmacology data as integral parts of this initiative. Previously, we reported that combining dynamic interactions between drugs and the rapid delayed rectifier potassium current (IKr) with multi-channel pharmacology is important for TdP risk classification, and we modified the original O'Hara Rudy ventricular cell mathematical model to include a Markov model of IKr to represent dynamic drug-IKr interactions (IKr-dynamic ORd model)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28877488/caveolae-in-rabbit-ventricular-myocytes-distribution-and-dynamic-diminution-after-cell%C3%A2-isolation
#12
Rebecca A B Burton, Eva A Rog-Zielinska, Alexander D Corbett, Rémi Peyronnet, Ilona Bodi, Martin Fink, Judith Sheldon, Andreas Hoenger, Sarah C Calaghan, Gil Bub, Peter Kohl
Caveolae are signal transduction centers, yet their subcellular distribution and preservation in cardiac myocytes after cell isolation are not well documented. Here, we quantify caveolae located within 100 nm of the outer cell surface membrane in rabbit single-ventricular cardiomyocytes over 8 h post-isolation and relate this to the presence of caveolae in intact tissue. Hearts from New Zealand white rabbits were either chemically fixed by coronary perfusion or enzymatically digested to isolate ventricular myocytes, which were subsequently fixed at 0, 3, and 8 h post-isolation...
September 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28875946/pva-dextran-hydrogel-patches-as-delivery-system-of-antioxidant-astaxanthin-a-cardiovascular-approach
#13
Marisol Zuluaga, Giulia Gregnanin, Claudia Cencetti, Chiara Di Meo, Virginie Gueguen, Didier Letourneur, Anne Meddahi-Pellé, Graciela Pavon-Djavid, Pietro Matricardi
After myocardial infarction, the heart's mechanical properties and its intrinsic capability to recover are compromised. To improve this recovery, several groups have developed cardiac patches based on different biomaterials strategies. Here, we developed polyvinylalcohol/dextran (PVA/Dex) elastic hydrogel patches, obtained through the freeze thawing (FT) process, with the aim to deliver locally a potent natural antioxidant molecule, astaxanthin, and to assist the heart's response against the generated myofibril stress...
September 6, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28875579/a-cardiac-patch-from-aligned-microvessel-and-cardiomyocyte-patches
#14
Jeremy A Schaefer, Pilar A Guzman, Sonja B Riemenschneider, Timothy J Kamp, Robert T Tranquillo
Cardiac tissue engineering aims to produce replacement tissue patches in the lab to replace or treat infarcted myocardium. However, current patches lack pre-formed microvascularization and are therefore limited in thickness and force production. In the present study, we sought to assess whether a bi-layer patch composed of a layer made from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a microvessel layer composed of self-assembled human blood outgrowth endothelial cells (BOECs) and pericytes (PCs) was capable of engrafting on the epicardial surface of a nude rat infarct model and becoming perfused by the host four weeks after acute implantation...
September 5, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28867785/patch-clamp-recording-from-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-improving-action-potential-characteristics-through-dynamic-clamp
#15
Arie O Verkerk, Christiaan C Veerman, Jan G Zegers, Isabella Mengarelli, Connie R Bezzina, Ronald Wilders
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in "ventricular-like" and "atrial-like" hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette)...
August 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28863155/electrophysiological-characteristics-of-pressure-overload-induced-cardiac-hypertrophy-and-its-influence-on-ventricular-arrhythmias
#16
Xiaowei Chen, Mu Qin, Weifeng Jiang, Yu Zhang, Xu Liu
OBJECTIVE: To explore the cardiac electrophysiological characteristics of cardiac hypertrophy and its influence on the occurrence of ventricular tachyarrhythmias. METHODS: Adult C57BL6 mice were randomly divided into a surgery group and a control group. Thoracic aortic constriction was performed on mice in the surgery group, and cardiac anatomical and ultrasonic evaluations were performed to confirm the success of the cardiac hypertrophy model 4 weeks after the operation...
2017: PloS One
https://www.readbyqxmd.com/read/28857082/basic-research-minimally-invasive-delivery-of-engineered-cardiac-patches-for-heart-repair
#17
Karina Huynh
No abstract text is available yet for this article.
October 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28855948/astragalus-granule-prevents-ca-2-current-remodeling-in-heart-failure-by-the-downregulation-of-camkii
#18
Sinai Li, Yibing Nong, Qun Gao, Jing Liu, Yan Li, Xiaoyun Cui, Jie Wan, Jinjin Lu, Mingjie Sun, Qian Wu, Xiaolu Shi, Haifeng Cui, Weihong Liu, Mingxue Zhou, Lina Li, Qian Lin
BACKGROUND: Astragalus was broadly used for treating heart failure (HF) and arrhythmias in East Asia for thousands of years. Astragalus granule (AG), extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca(2+) current (ICa-L) in HF mice by the downregulation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). METHODS: HF mice were induced by thoracic aortic constriction (TAC)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28854488/histological-and-biomechanical-characterization-of-decellularized-porcine-pericardium-as-a-potential-scaffold-for-tissue-engineering-applications
#19
Panagiotis Mallis, Efstathios Michalopoulos, Constantine Dimitriou, Nikolaos Kostomitsopoulos, Catherine Stavropoulos-Giokas
BACKGROUND: Each year, more than 800,000 vascular and cardiac surgeries are performed therefore, there is a great need for suitable material for bioprosthetic operations. Porcine pericardium is a double-walled sac that covers the heart and can be used in vascular and cardiac thoracic surgery. OBJECTIVE: The aim of the present study was to evaluate the decellularization process and biomechanical properties in porcine pericardial tissue after the decellularization treatment...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28832658/effects-of-equol-on-multiple-k-channels-stably-expressed-in-hek-293-cells
#20
Xiu-Ling Deng, Yan Wang, Guo-Sheng Xiao
The present study investigated the effects of equol on cardiovascular K+ channel currents. The cardiovascular K+ channel currents were determined in HEK 293 cells stably expressing cloned differential cardiovascular K+ channels with conventional whole-cell patch voltage-clamp technique. We found that equol inhibited hKv1.5 (IC50: 15.3 μM), hKv4.3 (IC50: 29.2 μM and 11.9 μM for hKv4.3 peak current and charge area, respectively), IKs (IC50: 24.7 μM) and IhERG (IC50: 31.6 and 56.5 μM for IhERG.tail and IhERG...
2017: PloS One
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