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https://www.readbyqxmd.com/read/29719087/regulation-of-inward-rectifier-potassium-current-ionic-channel-remodeling-by-at-1-calcineurin-nfat-signaling-pathway-in-stretch-induced-hypertrophic-atrial-myocytes
#1
Jionghong He, Yanan Xu, Long Yang, Guiling Xia, Na Deng, Yongyao Yang, Ye Tian, Zenan Fu, Yongqi Huang
Previous studies have shown that the activation of angiotensin II receptor type I (AT1 ) is attributed to cardiac remodeling stimulated by increased heart load, and that it is followed by the activation of the calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway. Additionally, AT1 has been found to be a regulator of cardiocyte ionic channel remodeling, and calcineurin-NFAT signals participate in the regulation of cardiocyte ionic channel expression. A hypothesis therefore follows that stretch stimulation may regulate cardiocyte ionic channel remodeling by activating the AT1 -calcineurin-NFAT pathway...
May 2, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29674971/a-numerical-study-of-scalable-cardiac-electro-mechanical-solvers-on-hpc-architectures
#2
Piero Colli Franzone, Luca F Pavarino, Simone Scacchi
We introduce and study some scalable domain decomposition preconditioners for cardiac electro-mechanical 3D simulations on parallel HPC (High Performance Computing) architectures. The electro-mechanical model of the cardiac tissue is composed of four coupled sub-models: (1) the static finite elasticity equations for the transversely isotropic deformation of the cardiac tissue; (2) the active tension model describing the dynamics of the intracellular calcium, cross-bridge binding and myofilament tension; (3) the anisotropic Bidomain model describing the evolution of the intra- and extra-cellular potentials in the deforming cardiac tissue; and (4) the ionic membrane model describing the dynamics of ionic currents, gating variables, ionic concentrations and stretch-activated channels...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29581825/novel-inhibitor-candidates-of-trpv2-prevent-damage-of-dystrophic-myocytes-and-ameliorate-against-dilated-cardiomyopathy-in-a-hamster-model
#3
Yuko Iwata, Yoshimi Katayama, Yasushi Okuno, Shigeo Wakabayashi
Transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a principal candidate for abnormal Ca2+ -entry pathways, which is a potential target for therapy of muscular dystrophy and cardiomyopathy. Here, an in silico drug screening and the following cell-based screening to measure the TRPV2 activation were carried out in HEK293 cells expressing TRPV2 using lead compounds (tranilast or SKF96365) and off-patent drug stocks. We identified 4 chemical compounds containing amino-benzoyl groups and 1 compound (lumin) containing an ethylquinolinium group as candidate TRPV2 inhibitors...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29529527/mechano-electric-finite-element-model-of-the-left-atrium
#4
Alessandro Satriano, Edward J Vigmond, David S Schwartzman, Elena S Di Martino
Mechanical stretch plays a major role in modulating atrial function, being responsible for beat-by-beat responses to changes in chamber preload, enabling a prompt regulation of cardiac function. Mechano-electric coupling (MEC) operates through many mechanisms and has many targets, making it experimentally difficult to isolate causes and effects especially under sinus conditions where effects are more transient and subtle. Therefore, modelling is a powerful tool to help understand the role of MEC with respect to the atrial electromechanical interaction...
May 1, 2018: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/29342222/mechano-electric-feedback-effects-in-a-three-dimensional-3d-model-of-the-contracting-cardiac-ventricle
#5
Ani Amar, Sharon Zlochiver, Ofer Barnea
Mechano-electric feedback affects the electrophysiological and mechanical function of the heart and the cellular, tissue, and organ properties. To determine the main factors that contribute to this effect, this study investigated the changes in the action potential characteristics of the ventricle during contraction. A model of stretch-activated channels was incorporated into a three-dimensional multiscale model of the contracting ventricle to assess the effect of different preload lengths on the electrophysiological behavior...
2018: PloS One
https://www.readbyqxmd.com/read/29305705/voltage-gated-and-stretch-activated-potassium-channels-in-the-human-heart-pathophysiological-and-clinical-significance
#6
REVIEW
Constanze Schmidt, Rémi Peyronnet
Ion channels are essential for electrical signaling and contractility in cardiomyocytes. Detailed knowledge about the molecular function and regulation of cardiac ion channels is crucial for understanding cardiac physiology and pathophysiology especially in the field of arrhythmias. This review aims at providing a general overview on the identity, functional characteristics, and roles of voltage-gated as well as stretch-activated potassium selective channels in the heart. In particular, we will highlight potential therapeutic targets as well as the emerging fields of future investigations...
March 2018: Herzschrittmachertherapie & Elektrophysiologie
https://www.readbyqxmd.com/read/29296068/morphological-dilemma-anomalous-pulmonary-venous-confluence-or-cor-triatriatum-does-it-matter
#7
Nagarajan Muthialu
Cardiac variant of total anomalous pulmonary venous return is a rare entity, whereby all the pulmonary veins drain directly to the right atrium or coronary sinus. The effective left heart blood flow channels through a small stretched patent foramen ovale and can often be confused with a variant of cor triatriatum. Cor triatriatum is a rare congenital cardiac anomaly where pulmonary veins drain to a persistent chamber above the left atrium with a membrane separating these two. There persists either a small aperture directly from the true to the accessory left atrium or none at all...
January 2018: Journal of the Saudi Heart Association
https://www.readbyqxmd.com/read/29282897/uniaxial-strain-of-cultured-mouse-and-rat-cardiomyocyte-strands-slows-conduction-more-when-its-axis-is-parallel-to-impulse-propagation-than-when-it-is-perpendicular
#8
A Buccarello, M Azzarito, F Michoud, S P Lacour, J P Kucera
AIM: Cardiac tissue deformation can modify tissue resistance, membrane capacitance and ion currents and hence cause arrhythmogenic slow conduction. Our aim was to investigate whether uniaxial strain causes different changes in conduction velocity (θ) when the principal strain axis is parallel vs perpendicular to impulse propagation. METHODS: Cardiomyocyte strands were cultured on stretchable custom microelectrode arrays, and θ was determined during steady-state pacing...
May 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29162778/ryanodine-receptor-type-2-plays-a-role-in-the-development-of-cardiac-fibrosis-under-mechanical-stretch-through-tgf%C3%AE-1
#9
Zhiwen Ding, Jie Yuan, Yanyan Liang, Jian Wu, Hui Gong, Yong Ye, Guoliang Jiang, Peipei Yin, Yang Li, Guoping Zhang, Chunjie Yang, Junjie Guo, Zhidan Chen, Xingxu Wang, Liqing Weng, Yunzeng Zou
Ryanodine receptor type 2 (RyR-2), the main Ca2+ release channel from sarcoplasmic reticulum in cardiomyocytes, plays a vital role in the regulation ofmyocardial contractile function and cardiac hypertrophy. However, the role of RyR-2 in cardiac fibrosis during the development of cardiac hypertrophy remains unclear.In this study, we examined whether RyR-2 regulates TGFβ1, which is secreted from cardiomyocytes and exerts on cardiac fibrosis using cultured cardiomyocytes and cardiac fibroblasts of neonatal rats...
December 12, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29131824/predictive-model-identifies-key-network-regulators-of-cardiomyocyte-mechano-signaling
#10
Philip M Tan, Kyle S Buchholz, Jeffrey H Omens, Andrew D McCulloch, Jeffrey J Saucerman
Mechanical strain is a potent stimulus for growth and remodeling in cells. Although many pathways have been implicated in stretch-induced remodeling, the control structures by which signals from distinct mechano-sensors are integrated to modulate hypertrophy and gene expression in cardiomyocytes remain unclear. Here, we constructed and validated a predictive computational model of the cardiac mechano-signaling network in order to elucidate the mechanisms underlying signal integration. The model identifies calcium, actin, Ras, Raf1, PI3K, and JAK as key regulators of cardiac mechano-signaling and characterizes crosstalk logic imparting differential control of transcription by AT1R, integrins, and calcium channels...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29126879/mechanical-stretch-increases-l-type-calcium-channel-stability-in-cardiomyocytes-through-a-polycystin-1-akt-dependent-mechanism
#11
A Córdova-Casanova, I Olmedo, J A Riquelme, G Barrientos, G Sánchez, T G Gillette, S Lavandero, M Chiong, P Donoso, Z Pedrozo
The L-type calcium channel (LTCC) is an important determinant of cardiac contractility. Therefore, changes in LTCC activity or protein levels could be expected to affect cardiac function. Several studies describing LTCC regulation are available, but only a few examine LTCC protein stability. Polycystin-1 (PC1) is a mechanosensor that regulates heart contractility and is involved in mechanical stretch-induced cardiac hypertrophy. PC1 was originally described as an unconventional Gi/o protein-coupled receptor in renal cells...
February 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28919864/%C3%AE-subunits-control-the-effects-of-human-kv4-3-potassium-channel-phosphorylation
#12
Geoffrey W Abbott
The transient outward K(+) current, Ito, activates early in the cardiac myocyte action potential, to begin repolarization. Human Ito is generated primarily by two Kv4.3 potassium channel α subunit splice variants (Kv4.3L and Kv4.3S) that diverge only by a C-terminal, membrane-proximal, 19-residue stretch unique to Kv4.3L. Protein kinase C (PKC) phosphorylation of threonine 504 within the Kv4.3L-specific 19-residues mediates α-adrenergic inhibition of Ito in human heart. Kv4.3 is regulated in human heart by various β subunits, including cytosolic KChIP2b and transmembrane KCNEs, yet their impact on the functional effects of human Kv4...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28702845/regulation-of-cardiac-ca-2-and-ion-channels-by-shear-mechanotransduction
#13
REVIEW
Joon-Chul Kim, Min-Jeong Son, Jun Wang, Sun-Hee Woo
Cardiac contraction is controlled by a Ca2+ signaling sequence that includes L-type Ca2+ current-gated opening of Ca2+ release channels (ryanodine receptors) in the sarcoplasmic reticulum (SR). Local Ca2+ signaling in the atrium differs from that in the ventricle because atrial myocytes lack transverse tubules and have more abundant corbular SR. Myocardium is subjected to a variety of forces with each contraction, such as stretch, shear stress, and afterload, and adapts to those mechanical stresses. These mechanical stimuli increase in heart failure, hypertension, and valvular heart diseases that are clinically implicated in atrial fibrillation and stroke...
July 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28645743/role-of-trpc3-and-trpc6-channels-in-the-myocardial-response-to-stretch-linking-physiology-and-pathophysiology
#14
REVIEW
Yohei Yamaguchi, Gentaro Iribe, Motohiro Nishida, Keiji Naruse
Transient receptor potential (TRP) channels constitute a large family of versatile multi-signal transducers. In particular, TRP canonical (TRPC) channels are known as receptor-operated, non-selective cation channels. TRPC3 and TRPC6, two members in the TRPC family, are highly expressed in the heart, and participate in the pathogenesis of cardiac hypertrophy and heart failure as a pathological response to chronic mechanical stress. In the pathological response, myocardial stretch increases intracellular Ca2+ levels and activates nuclear factor of activated T cells to induce cardiac hypertrophy...
November 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28546113/stretch-activated-trpv2-channels-role-in-mediating-cardiopathies
#15
REVIEW
Elizabeth Aguettaz, Patrick Bois, Christian Cognard, Stéphane Sebille
Transient receptor potential vanilloid type 2, TRPV2, is a calcium-permeable cation channel belonging to the TRPV channel family. Although this channel has been first characterized as a noxious heat sensor, its mechanosensor property recently gained importance in various physiological functions. TRPV2 has been described as a stretch-mediated channel and a regulator of calcium homeostasis in several cell types and has been shown to be involved in the stretch-dependent responses in cardiomyocytes. Hence, several studies in the last years support the idea that TRPV2 play a key role in the function and structure of the heart, being involved in the cardiac compensatory mechanisms in response to pathologic or exercise-induced stress...
November 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28526353/stretch-activated-two-pore-domain-k-2p-potassium-channels-in-the-heart-focus-on-atrial-fibrillation-and-heart-failure
#16
Constanze Schmidt, Felix Wiedmann, Stefan M Kallenberger, Antonius Ratte, Jan S Schulte, Beatrix Scholz, Frank Ulrich Müller, Niels Voigt, Maria-Patapia Zafeiriou, Joachim R Ehrlich, Ursula Tochtermann, Gábor Veres, Arjang Ruhparwar, Matthias Karck, Hugo A Katus, Dierk Thomas
Two-pore-domain potassium (K2P ) channels modulate cellular excitability. The significance of stretch-activated cardiac K2P channels (K2P 2.1, TREK-1, KCNK2; K2P 4.1, TRAAK, KCNK4; K2P 10.1, TREK-2, KCNK10) in heart disease has not been elucidated in detail. The aim of this work was to assess expression and remodeling of mechanosensitive K2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models. Cardiac K2P channel levels were quantified in atrial (A) and ventricular (V) tissue obtained from patients undergoing open heart surgery...
November 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28526352/stretch-activated-potassium-currents-in-the-heart-focus-on-trek-1-and-arrhythmias
#17
REVIEW
Niels Decher, Aytug K Kiper, Susanne Rinné
This review focuses on the role and the molecular candidates of the cardiac stretch-activated potassium current (SAK). The functional properties of the two-pore domain potassium (K2P ) channel TREK-1, a major candidate for the cardiac SAK, are analyzed and the molecular mechanism of stretch-activation in K2P potassium channels is discussed. Furthermore, the functional modulation of TREK-1 by different cardiac interaction partners, as well as evidence for the functional role of the stretch-dependent TREK-1 and its putative subunits in the heart is reviewed...
November 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28510575/electro-mechanical-dynamics-of-spiral-waves-in-a-discrete-2d-model-of-human-atrial-tissue
#18
Paul Brocklehurst, Haibo Ni, Henggui Zhang, Jianqiao Ye
We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER) of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM). Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28502667/mechanosensitivity-from-aristotle-s-sense-of-touch-to-cardiac-mechano-electric-coupling
#19
REVIEW
Johann P Kuhtz-Buschbeck, Jochen Schaefer, Nicolaus Wilder
Scientific interest in mechanosensation likely commenced with Aristotle's description of the sense of touch in his treatise de Anima [On the Soul]. Considering touch as a vital sense distributed over the whole body, the philosopher outlined a "physiological concept" at the macro-level already 2400 years ago. From this starting point, we outline the onset of modern sensory physiology during the early 19th century. Physiologists distinguished between outer and inner senses at that time, without, however, referring to specific receptors or nerves...
November 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28483598/the-mechano-sensitivity-of-cardiac-atp-sensitive-potassium-channels-is-mediated-by-intrinsic-mgatpase-activity
#20
Mohammad Fatehi, Christian C Carter, Nermeen Youssef, Peter E Light
Cardiac ATP-sensitive K+ (KATP ) channel activity plays an important cardio-protective role in regulating excitability in response to metabolic stress. Evidence suggests that these channels are also mechano-sensitive and therefore may couple KATP channel activity to increased cardiac workloads. However, the molecular mechanism that couples membrane stretch to channel activity is not currently known. We hypothesized that membrane stretch may alter the intrinsic MgATPase activity of the cardiac KATP channel resulting in increased channel activation...
July 2017: Journal of Molecular and Cellular Cardiology
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