scholarly journals Arrhythmogenesis in heart cells involves reverse E–C coupling and reverse electrotonic conduction along T-tubules

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Takao Shioya
Keyword(s):  
Causal Link ◽  
Mouse Heart ◽  
Heart Cells ◽  
Cellular Mechanisms ◽  
Reverse Mode ◽  
Early Afterdepolarization ◽  
Action Potential Plateau ◽  
Length Constant ◽  
Life Threatening ◽  
T Tubules

Early afterdepolarization (EAD) is an aberrant cardiac afterpotential that underlies the development of life-threatening ventricular arrhythmias. It is believed that the development of EAD is caused by the reactivation of L-type Ca2+ current during the period of the action potential plateau; however, the cellular mechanisms that underlie the development of EAD is still controversial. One favorable alternative is the depolarizing reverse-mode operation of the Na+/Ca2+ exchanger, which is activated by aberrant Ca2+ release from the sarcoplasmic reticulum in the process of reverse E–C coupling. Since EADs develop preferentially in damaged heart cells with abnormal Ca2+-signaling, here I studied the causal link between the development of EADs and aberrant intracellular Ca2+ level ([Ca2+]i) dynamics in mouse heart cells using the whole-cell clamp technique. My results show (1) the generation of EADs was preceded by the development of depolarizing membrane potential (Vm) fluctuation, (2) the depolarizing Vm fluctuation is associated with [Ca2+]i elevation, suggesting an involvement of reverse E–C coupling via the Na+/Ca2+ exchanger, and (3) that extending the T-tubules’ length constant by decreasing the extracellular K+ level facilitated the development of the Vm fluctuation and EADs. Taken together, I conclude that EADs are caused by the depolarizing Vm fluctuation, which is induced locally in the T-tubule membrane by aberrant [Ca2+]i elevation and is conducted back electrotonically along the T-tubules.

scholarly journals Review: Toll-like receptors and NOD-like receptors in pulmonary antibacterial immunity

2010 ◽  
Vol 16 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Theivanthiran Balamayooran ◽  
Gayathriy Balamayooran ◽  
Samithamby Jeyaseelan
Keyword(s):  
Distress Syndrome ◽  
Bacterial Pathogens ◽  
Treatment Strategies ◽  
Lung Damage ◽  
Toll Like Receptors ◽  
Neutrophil Accumulation ◽  
Cellular Mechanisms ◽  
Neutrophil Influx ◽  
Life Threatening ◽  
Parenchymal Damage

Lung diseases caused by bacteria are a leading cause of death in both immunocompromised and immunocompetent individuals as well as in children. Although neutrophil recruitment is critical to augment the host defence, excessive neutrophil accumulation results in life-threatening diseases, such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Therefore, it is important to modulate excessive neutrophil influx in ALI/ARDS to mitigate lung damage and mortality. A better understanding of the basic mechanisms underlying neutrophil influx is crucial to designing novel and innovative treatment strategies for ALI/ARDS. Recognition of bacteria in the lung is the critical first step leading to neutrophil influx. Pattern recognition receptors, such as Toll-like receptors and NOD-like receptors, play an important role in the recognition of bacterial pathogens. Understanding the molecular and cellular mechanisms associated with the recognition of bacterial pathogens by the host is critical for the development of effective therapeutic strategies to control parenchymal damage via modulating neutrophil accumulation in the lung.

scholarly journals Molecular regulation of myocardial proliferation and regeneration

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lixia Zheng ◽  
Jianyong Du ◽  
Zihao Wang ◽  
Qinchao Zhou ◽  
Xiaojun Zhu ◽  
...  
Keyword(s):  
Recent Literature ◽  
Biological Process ◽  
Cardiac Regeneration ◽  
Molecular Regulation ◽  
Mouse Heart ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Cellular Mechanisms ◽  
Concise Review ◽  
Complex Biological Process

AbstractHeart regeneration is a fascinating and complex biological process. Decades of intensive studies have revealed a sophisticated molecular network regulating cardiac regeneration in the zebrafish and neonatal mouse heart. Here, we review both the classical and recent literature on the molecular and cellular mechanisms underlying heart regeneration, with a particular focus on how injury triggers the cell-cycle re-entry of quiescent cardiomyocytes to replenish their massive loss after myocardial infarction or ventricular resection. We highlight several important signaling pathways for cardiomyocyte proliferation and propose a working model of how these injury-induced signals promote cardiomyocyte proliferation. Thus, this concise review provides up-to-date research progresses on heart regeneration for investigators in the field of regeneration biology.

scholarly journals Endosome-Mediated Epithelial Remodeling Downstream of Hedgehog/Gli Is Required for Tracheoesophageal Separation

2019 ◽  
Author(s):  
Talia Nasr ◽  
Pamela Mancini ◽  
Scott A. Rankin ◽  
Nicole A. Edwards ◽  
Zachary N. Agricola ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Birth Defects ◽  
Small Gtpase ◽  
List Type ◽  
Matrix Degradation ◽  
Cellular Mechanisms ◽  
Extracellular Matrix Degradation ◽  
Cellular Basis ◽  
Life Threatening ◽  
Epithelial Remodeling

SUMMARYThe trachea and esophagus arise from the separation of a common foregut tube during early fetal development. Mutations in key signaling pathways such as Hedgehog (HH)/Gli can disrupt tracheoesophageal (TE) morphogenesis and cause life-threatening birth defects (TEDs), however the underlying cellular mechanisms are unknown. Here we use mouse and Xenopus to define the HH/Gli-dependent processes orchestrating TE morphogenesis. We show that downstream of Gli the Foxf1+ splanchnic mesenchyme promotes medial constriction of the foregut at the boundary between the presumptive Sox2+ esophageal and Nkx2-1+ tracheal epithelium. We identify a unique boundary epithelium co-expressing Sox2 and Nkx2-1 that fuses to form a transient septum. Septum formation and resolution into distinct trachea and esophagus requires endosome-mediated epithelial remodeling involving the small GTPase Rab11, and localized extracellular matrix degradation. These are disrupted in Gli-deficient embryos. This work provides a new mechanistic framework for TE morphogenesis and informs the cellular basis of human TEDs.Highlight bullet pointsThe Sox2+ esophagus and Nkx2-1+ trachea arise from the separation of a single foregut tube through a series of cellular events conserved in mouse and XenopusTracheoesophageal morphogenesis initiates with HH/Gli-dependent medial constriction of the gut tube mesenchyme at the Sox2-Nkx2-1 borderThe foregut epithelial walls fuse forming a transient septum co-expressing Sox2 and Nkx2-1Downstream of HH/Gli Rab11-dependent endosome-mediated epithelial remodeling and localized extracellular matrix degradation separate the esophagus and tracheaHH/Gli mutations reveal the cellular basis of tracheoesophageal birth defects

scholarly journals The Clinical Perspective on Hepatitis E

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 617 ◽  
Author(s):  
Thomas Horvatits ◽  
Julian Schulze zur Wiesch ◽  
Marc Lütgehetmann ◽  
Ansgar W. Lohse ◽  
Sven Pischke
Keyword(s):  
Liver Failure ◽  
Hepatitis E ◽  
Causal Link ◽  
Chronic Liver ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Chronic Liver Failure ◽  
Industrialized Nations ◽  
Life Threatening ◽  
The Tropics

Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible.

Simulation of Ca 2+ -activated Cl − current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca 2+ dynamics

2006 ◽  
Vol 364 (1842) ◽  
pp. 1223-1243 ◽  
Author(s):  
Chae Hun Leem ◽  
Won Tae Kim ◽  
Jeong Mi Ha ◽  
Yoon Jin Lee ◽  
Hyeon Chan Seong ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Pulmonary Vein ◽  
Ryanodine Receptor ◽  
Diffusion Coefficients ◽  
Atrial Myocytes ◽  
Reverse Mode ◽  
Step Voltage ◽  
Outward Currents ◽  
T Tubules ◽  
The Stability

In recent studies, we recorded transiently activated outward currents by the application of three-step voltage pulses to induce a reverse mode of Na + –Ca 2+ exchange (NCX). We found that these currents were mediated by a Ca 2+ -activated Cl − current. Based on the recent reports describing the atrial Ca 2+ transients, the Ca 2+ transient at the subsarcolemmal space was initiated and then diffused into the cytosolic space. Because the myocardium in the pulmonary vein is an extension of the atrium, the Ca 2+ -activated Cl − current may reflect the subsarcolemmal Ca 2+ dynamics. We tried to predict the subsarcolemmal Ca 2+ dynamics by simulating these current traces. According to recent reports on the geometry of atrial myocytes, we assumed that there were three compartments of sarcoplasmic reticulum (SR): a network SR, a junctional SR and a central SR. Based on these structures, we also divided the cytosolic space into three compartments: the junctional, subsarcolemmal and cytosolic spaces. Geometry information and cellular capacitance suggested that there were essentially no T-tubules in these cells. The basic physical data, such as the compartmental volumes, the diffusion coefficients and the stability coefficients of the Ca 2+ buffers, were obtained from the literature. In the simulation, we incorporated the NCX, the L-type Ca 2+ channel, the rapid activating outward rectifier K + channel, the Na + –K + pump, the SR Ca 2+ -pump, the ryanodine receptor, the Ca 2+ -activated Cl − channel and the dynamics of Na + , K + , Ca 2+ and Cl − . In these conditions, we could successfully reconstruct the Ca 2+ -activated Cl − currents. The simulation allowed estimation of the Ca 2+ dynamics of each compartment and the distribution of the Ca 2+ -activated Cl − channel and the NCX in the sarcolemma on the junctional or subsarcolemmal space.

Genetic Toxicity of Berberine on Mouse Heart

2014 ◽  
Vol 884-885 ◽  
pp. 634-637
Author(s):  
Cheng Bin Xu ◽  
Lu Wang ◽  
Xiu Juan Hui ◽  
Xi Ping Ma ◽  
Xin Bi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Medicine ◽  
Tail Length ◽  
Dose Effect ◽  
Mouse Heart ◽  
Heart Cells ◽  
Tail Moment ◽  
Biochemical Responses ◽  
Common Drug ◽  
Change Tendency

Berberine, a common drug, which is widely used in clinical medicine as inflammatory medicines, is rarely studied about its affection on non-target organisms in recent researches. To evaluate the eco-toxicity of berberine in mouse heart cells, biochemical responses including oxidative damage and changes in the activities of antioxidative enzymes catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and malondialdehyde (MDA) induced by berberine were investigated in mouse heart cells. 7.5, 15, 30, 60 and 120 mgkg-1 berberine was added to mouse heart cells respectively. Compared to the controls, the damage, tail DNA content (%) , tail length and tail moment went up respectively in dose-effect manner following the rising berberine; As the content of berberine increased, the activities of SOD, CAT and POD were gradually decreased and the concentration of MDA was gradually increased. Compared to the controls, the change tendency showed significant differences (p<0.05 or p<0.01). In conclusion, berberine induces oxidative stress and DNA damage to heart cells, which may be the significant mechanisms for its toxicity to mice.

scholarly journals Systemic and vascular inflammation in an in-vitro model of central obesity

2017 ◽  
Author(s):  
A. Ahluwalia ◽  
A. Misto ◽  
F. Vozzi ◽  
C. Magliaro ◽  
G. Mattei ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Vascular Inflammation ◽  
Animal Experiments ◽  
Causal Link ◽  
Tissue Response ◽  
Central Adiposity ◽  
Cellular Mechanisms ◽  
Vitro Model ◽  
Set Up

AbstractMetabolic disorders due to over-nutrition are a major global health problem, often associated with obesity and related morbidities. Obesity is peculiar to humans, as it is associated with lifestyle and diet, and so difficult to reproduce in animal models.Here we describe a model of human central adiposity based on a 3-tissue system consisting of a series of interconnected fluidic modules. Given the causal link between obesity and systemic inflammation, we focused primarily on pro-inflammatory markers, examining the similarities and differences between the 3-tissue model and evidence from human studies in the literature. When challenged with high levels of adiposity, the in-vitro system manifests cardiovascular stress through expression of E-selectin and von Willebrand factor as well as systemic inflammation (expressing IL-6 and MCP-1) as observed in humans. Interestingly, most of the responses are dependent on the synergic interaction between adiposity and the presence of multiple tissue types. The set-up has the potential to reduce animal experiments in obesity research and may help unravel specific cellular mechanisms which underlie tissue response to nutritional overload.

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