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https://www.readbyqxmd.com/read/28229450/endogenous-nitric-oxide-formation-in-cardiac-myocytes-does-not-control-respiration-during-%C3%AE-adrenergic-stimulation
#1
Michael Kohlhaas, Alexander G Nickel, Stefanie Bergem, Barbara Casadei, Ulrich Laufs, Christoph Maack
Endothelial nitric oxide (NO) controls cardiac oxygen (O2 ) consumption in a paracrine way by slowing respiration at the mitochondrial electron transport chain. While NO synthases (NOS) are also expressed in cardiac myocytes, it is unclear whether they control respiration in an intracrine way. Furthermore, the existence of a mitochondrial NOS is controversial. Here, by combining fluorescence imaging with electrical field stimulation, the patch-clamp method and knock-out technology, we determined the sources and consequences of intracellular NO formation during workload transitions in isolated murine and guinea pig cardiac myocytes and mitochondria...
February 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28228734/%C3%AE-subunits-functionally-differentiate-human-kv4-3-potassium-channel-splice-variants
#2
Geoffrey W Abbott
The human ventricular cardiomyocyte transient outward K(+) current (Ito) mediates the initial phase of myocyte repolarization and its disruption is implicated in Brugada Syndrome and heart failure (HF). Human cardiac Ito is generated primarily by two Kv4.3 splice variants (Kv4.3L and Kv4.3S, diverging only by a C-terminal, S6-proximal, 19-residue stretch unique to Kv4.3L), which are differentially remodeled in HF, but considered functionally alike at baseline. Kv4.3 is regulated in human heart by β subunits including KChIP2b and KCNEs, but their effects were previously assumed to be Kv4...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28227776/propagation-of-parametric-uncertainty-for-the-k-channel-model-in-mouse-ventricular-myocytes
#3
Yuncheng Du, Dongping Du, Yuncheng Du, Dongping Du, Dongping Du, Yuncheng Du
Cardiac potassium (K+) channel plays an important role in cardiac electrical signaling. Mathematical models have been widely used to investigate the effects of K+ channels on cardiac functions. However, the model of K+ channel involves parametric uncertainties, which can be induced by fitting the model's parameters that best capture experimental data. Since the prediction of cardiac functions are highly parameter-dependent, it is critical to quantify the influence of parametric uncertainty on the model responses to provide the more reliable predictions...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226464/modulation-of-cardiac-pacemaker-inter-beat-intervals-by-sinoatrial-fibroblasts-a-numerical-study
#4
Ariel Greisas, Sharon Zlochiver, Ariel Greisas, Sharon Zlochiver, Ariel Greisas, Sharon Zlochiver
The potential effect of sinoatrial fibroblasts on beat rate and variability of the cardiac pacemakers is not yet fully understood. Heterocellular coupling formation and fibroblast proliferation during diseased conditions may further signify the impact of those cells on sinoatrial node function. In this study we numerically modeled the impact of varying numbers of fibroblasts that are electrically coupled to a single pacemaker cell on several electrophysiological parameters. We employed cellular kinetics of the rabbit sinoatrial myocyte, and employed a range of potential gap junctional coupling between fibroblasts and myocytes...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226461/role-of-cytosolic-calcium-diffusion-in-cardiac-purkinje-cells
#5
Bijay Limbu, Kushal Shah, Makarand Deo, Bijay Limbu, Kushal Shah, Makarand Deo, Bijay Limbu, Makar Deo, Kushal Shah
The Cardiac Purkinje cells (PCs) exhibit distinct calcium (Ca(2)+) homeostasis than that in ventricular myocytes (VMs). Due to lack of t-tubules in PCs, the Ca(2)+ ions entering the cell have to diffuse through the cytoplasm to reach the sarcoplasmic reticulum (SR) before triggering Ca(2)+-induced-Ca(2)+-release (CICR). In recent experimental studies PCs have been shown to be more susceptible to action potential (AP) abnormalities than the VMs, however the exact mechanisms are poorly understood. In this study, we utilize morphologically realistic detailed biophysical mathematical model of a murine PC to systematically examine the role intracellular Ca(2)+ diffusion in the APs of PCs...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#6
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223475/reduced-first-phase-ejection-fraction-and-sustained-myocardial-wall-stress-in-hypertensive-patients-with-diastolic-dysfunction-a-manifestation-of-impaired-shortening-deactivation-that-links-systolic-to-diastolic-dysfunction-and-preserves-systolic-ejection-fraction
#7
Haotian Gu, Ye Li, Henry Fok, John Simpson, Jonathan C Kentish, Ajay M Shah, Philip J Chowienczyk
Impaired shortening deactivation of cardiac myocytes could sustain myocardial contraction, preserving ejection fraction at the expense of diastolic dysfunction. We examined the relationship between first-phase ejection fraction (EF1), the fraction of left ventricular volume ejected from the start of systole to the time of the first peak in left ventricular pressure (corresponding to the time of maximal ventricular shortening) to the duration of myocardial contraction and diastolic function in patients with hypertension (n=163), and varying degrees of diastolic dysfunction...
February 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28223230/myotoxicity-of-statins-mechanism-of-action
#8
REVIEW
Patrick du Souich, Ghislaine Roederer, Robert Dufour
Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia; however, they cause frequent undesirable side effects. The incidence of statin-induced myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report. SIM may develop in presence of abnormally high concentrations of statins in the myocyte and/or in presence of muscular conditions that may predispose to SIM. High concentrations of statins in the myocyte may occur whenever the activity of liver influx membrane transporters, namely OATP1B1, of drug metabolizing enzymes, and of liver and muscular efflux transporters, MDR1 and BCRP, is reduced...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28223225/the-control-of-cardiac-ventricular-excitability-by-autonomic-pathways
#9
REVIEW
Malcolm Finlay, Stephen C Harmer, Andrew Tinker
Central to the genesis of ventricular cardiac arrhythmia are variations in determinants of excitability. These involve individual ionic channels and transporters in cardiac myocytes but also tissue factors such as variable conduction of the excitation wave, fibrosis and source-sink mismatch. It is also known that in certain diseases and particularly the channelopathies critical events occur with specific stressors. For example, in hereditary long QT syndrome due to mutations in KCNQ1 arrhythmic episodes are provoked by exercise and in particular swimming...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222055/ex-situ-perfusion-of-human-limb-allografts-for-24-hours
#10
Nicole L Werner, Fares Alghanem, Stephanie L Rakestraw, Dylan C Sarver, Bruce Nicely, Richard E Pietroski, Paul Lange, Steven M Rudich, Christopher L Mendias, Alvaro Rojas-Pena, John C Magee, Robert H Bartlett, Kagan Ozer
BACKGROUND: Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. METHODS: Upper limbs were procured from brain-dead organ donors...
March 2017: Transplantation
https://www.readbyqxmd.com/read/28219977/adrenergic-receptors-in-individual-ventricular-myocytes-the-beta-1-and-alpha-1b-are-in-all-cells-the-alpha-1a-is-in-a-subpopulation-and-the-beta-2-and-beta-3-are-mostly-absent
#11
Bat-Erdene Myagmar, James M Flynn, Patrick M Cowley, Philip Swigart, Megan Montgomery, Kevin Thai, Divya R Nair, Rumita Gupta, Chihiro Hosoda, Simon Melov, Anthony J Baker, Paul C Simpson
Rationale: It is unknown if every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), beta-1, beta-2, beta-3, alpha-1A, and alpha-1B. The beta-1 and beta-2 are thought to be the dominant myocyte ARs. Objective: Quantify the 5 cardiac ARs in individual ventricular myocytes. Methods and Results: We studied ventricular myocytes from wild type mice, mice with alpha-1A and alpha-1B knockin reporters, and beta-1 and beta-2 knockout mice. Using individual isolated cells, we measured knockin reporters, mRNAs, signaling (phosphorylation of ERK and phospholamban), and contraction...
February 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28219356/bacopa-monnieri-extract-increases-rat-coronary-flow-and-protects-against-myocardial-ischemia-reperfusion-injury
#12
Sirintorn Srimachai, Sylvie Devaux, Celine Demougeot, Sarawut Kumphune, Nina D Ullrich, Ernst Niggli, Kornkanok Ingkaninan, Natakorn Kamkaew, C Norman Scholfield, Sompol Tapechum, Krongkarn Chootip
BACKGROUND: This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. METHODS: In normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 μg/ml B...
February 20, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28219158/-experimental-observation-on-the-histopathological-and-ultrastructural-pathology-of-great-gerbils-rhombomys-opimus-in-the-junggar-basin-by-subcutaneous-injecting-of-yersinia-pestis
#13
B Li, Rehemu Azhati, W W Meng, T Luo, B Li, Maituohuti Abulimiti, X H Wang, X Dai, Y J Zhang
Objective: To understand the histopathological and ultrastructural pathology changes of great gerbils in the Junggar Basin to Yersinia pestis infection. Methods: Forty captured great gerbils from the Junggar Basin that tested negative for anti-F1 antibodies were infected. The Y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the Junggar Basin in 2005 with a median lethal dose (LD(50)) of <10 CFU/ml, was used in this study. Forty great gerbils were divided into seven infection groups and were subcutaneously infected with 7...
February 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28217315/gemcitabine-induced-cardiomyopathy-a-case-of-multiple-hit-cardiotoxicity
#14
Donya Mohebali, Jason Matos, James Ducksoon Chang
Gemcitabine is a commonly used antineoplastic agent used to treat a variety of cancers with rarely reported cardiac side effects. We describe a case of a 67-year-old woman with follicular lymphoma who experienced a rarely reported side effect of gemcitabine: cardiomyopathy. This case highlights a multiple hit mechanism of myocyte damage that may occur following the use of multiple cardio-toxic agents despite their administration in doses not associated with cardiotoxicity.
February 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28214885/signaling-pathway-for-endothelin-1-and-phenylephrine-induced-camp-response-element-binding-protein-activation-in-rat-ventricular-myocytes-role-of-inositol-1-4-5-trisphosphate-receptors-and-camkii
#15
Krishna P Subedi, Min-Jeong Son, Bojjibabu Chidipi, Seong-Woo Kim, Jun Wang, Kyeong-Hee Kim, Sun-Hee Woo, Joon-Chul Kim
BACKGROUND/AIMS: Endothelin-1 (ET-1) and the α<Sub>1</Sub>-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understood. We examined signaling pathways for ET-1- or PE-induced cardiac CREB activation. METHODS: Western blotting was performed with pharmacological and genetic interventions in rat ventricular myocytes...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214847/contribution-of-p62-to-phenotype-transition-of-coronary-arterial-myocytes-with-defective-autophagy
#16
Junxiang Bao, Guangbi Li, Xinxu Yuan, Erich Gulbins, Pin-Lan Li
BACKGROUND: Autophagy disorder contributes to dedifferentiation of arterial smooth muscle cells, but the mechanisms are poorly understood. Here, we sought to investigate the role of scaffolding adaptor p62/SQSTM1 (p62) in phenotype switching of mouse coronary arterial myocytes (CAMs) induced by CD38 gene deficiency or lysosomal dysfunction which blocks autophagic flux in the cells. METHODS: Protein expression was measured by western blot analysis and immunofluorescent staining...
3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213753/electrophysiologic-studies-on-the-risks-and-potential-mechanism-underlying-the-proarrhythmic-nature-of-azithromycin
#17
Mengdan Zhang, Ming Xie, Sha Li, Ying Gao, Shuyin Xue, Huili Huang, Kesu Chen, Fuming Liu, Long Chen
The mechanisms underlying arrhythmia induced by the clinical use of azithromycin are poorly understood. We aimed to investigate the proarrhythmic effects of azithromycin using electrocardiogram (ECG) and ion channel models. In vivo and in vitro guinea pig ECG and current and voltage clamp recordings were carried out. Azithromycin at 114.6 mg/kg (three times the clinically relevant dose) reduced heart rate (HR) and prolonged the PR, QRS and rate-corrected QT (QTc) intervals of guinea pig ECG in vivo. In vitro technique revealed that azithromycin at 207...
February 17, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28213505/revealing-the-concealed-nature-of-long-qt-type-3-syndrome
#18
Amara Greer-Short, Sharon A George, Steven Poelzing, Seth H Weinberg
BACKGROUND: Gain-of-function mutations in the voltage-gated sodium channel (Nav1.5) are associated with the long-QT-3 (LQT3) syndrome. Nav1.5 is densely expressed at the intercalated disk, and narrow intercellular separation can modulate cell-to-cell coupling via extracellular electric fields and depletion of local sodium ion nanodomains. Models predict that significantly decreasing intercellular cleft widths slows conduction because of reduced sodium current driving force, termed "self-attenuation...
February 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28213332/shear-stress-enhances-ca-2-sparks-through-nox2-dependent-mitochondrial-reactive-oxygen-species-generation-in-rat-ventricular-myocytes
#19
Joon-Chul Kim, Jun Wang, Min-Jeong Son, Sun-Hee Woo
Shear stress enhances diastolic and systolic Ca(2+) concentration in ventricular myocytes. Here, using confocal Ca(2+) imaging in rat ventricular myocytes, we assessed the effects of shear stress (~16dyn/cm(2)) on the frequency of spontaneous Ca(2+) sparks and explored the mechanism underlying shear-mediated Ca(2+) spark regulation. The frequency of Ca(2+) sparks was immediately increased by shear stress (by ~80%), and increased further (by ~150%) during prolonged exposure (20s). The 2-D size and duration of individual sparks were increased by shear stimulation...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213290/zd0947-a-sulphonylurea-receptor-modulator-detects-functional-sulphonylurea-receptor-subunits-in-murine-vascular-smooth-muscle-atp-sensitive-k-channels
#20
Tadashi Yamamoto, Kohei Takahara, Keiichiro Uchida, Noriyoshi Teramoto
In order to identify functional sulphonylurea receptor (SUR.x) subunits of native ATP-sensitive K(+) channels (KATP channels) in mouse portal vein, the effects of ZD0947, a SUR.x modulator, were investigated on spontaneous portal vein contractions, macroscopic membrane currents and unitary currents recorded (using patch-clamp techniques) in freshly dispersed mouse portal vein myocytes. Spontaneous contractions in mouse portal vein were reversibly reduced by ZD0947 in a concentration-dependent manner (Ki = 293nM)...
February 14, 2017: European Journal of Pharmacology
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