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https://www.readbyqxmd.com/read/28546113/stretch-activated-trpv2-channels-role-in-mediating-cardiopathies
#1
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...
May 22, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28526353/stretch-activated-two-pore-domain-k2p-potassium-channels-in-the-heart-focus-on-atrial-fibrillation-and-heart-failure
#2
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 (K2P2.1, TREK-1, KCNK2; K2P4.1, TRAAK, KCNK4; K2P10.1, 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...
May 16, 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
#3
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...
May 16, 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
#4
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
#5
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...
May 11, 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
#6
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...
May 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28402883/a-role-of-bk-channel-in-regulation-of-ca-2-channel-in-ventricular-myocytes-by-substrate-stiffness
#7
Hucheng Zhao, Yang Yu, Xiaoan Wu, Sisi Liu, Bailin Liu, Jing Du, Bo Li, Linhua Jiang, Xiqiao Feng
Substrate stiffness is crucial for diverse cell functions, but the mechanisms conferring cells with mechanosensitivity are still elusive. By tailoring substrate stiffness with 10-fold difference, we showed that L-type voltage-gated Ca(2+) channel current density was greater in chick ventricular myocytes cultured on the stiff substrate than on the soft substrate. Blockage of the BK channel increased the Ca(2+) current density on the soft substrate and consequently eliminated substrate stiffness regulation of the Ca(2+) channel...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28381704/efficacy-of-precordial-percussion-pacing-assessed-in-a-cardiac-standstill-microminipig-model
#8
Takeshi Wada, Hiroshi Ohara, Yuji Nakamura, Xin Cao, Hiroko Izumi-Nakaseko, Kentaro Ando, Mitsuru Honda, Katsunori Yoshihara, Yuji Nakazato, Keith G Lurie, Atsushi Sugiyama
BACKGROUND: Potential cardiovascular benefits of precordial percussion pacing (PPP) during cardiac standstill are unknown.Methods and Results:A cardiac standstill model in amicrominipigwas created by inducing complete atrioventricular block with a catheter ablation technique (n=7). Next, the efficacy of cardiopulmonary resuscitation by standard chest compressions (S-CPR), PPP and ventricular electrical pacing in this model were analyzed in series (n=4). To assess the mechanism of PPP, a non-selective, stretch-activated channel blocker, amiloride, was administered during PPP (n=3)...
April 4, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28228734/%C3%AE-subunits-functionally-differentiate-human-kv4-3-potassium-channel-splice-variants
#9
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/28105583/trpc3-participates-in-angiotensin-ii-type-1-receptor-dependent-stress-induced-slow-increase-in-intracellular-ca-2-concentration-in-mouse-cardiomyocytes
#10
Yohei Yamaguchi, Gentaro Iribe, Toshiyuki Kaneko, Ken Takahashi, Takuro Numaga-Tomita, Motohiro Nishida, Lutz Birnbaumer, Keiji Naruse
When a cardiac muscle is held in a stretched position, its [Ca(2+)] transient increases slowly over several minutes in a process known as stress-induced slow increase in intracellular Ca(2+) concentration ([Ca(2+)]i) (SSC). Transient receptor potential canonical (TRPC) 3 forms a non-selective cation channel regulated by the angiotensin II type 1 receptor (AT1R). In this study, we investigated the role of TRPC3 in the SSC. Isolated mouse ventricular myocytes were electrically stimulated and subjected to sustained stretch...
January 19, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28009703/transient-receptor-potential-vanilloid-2-function-regulates-cardiac-hypertrophy-via-stretch-induced-activation
#11
Sheryl E Koch, Adrien Mann, Shannon Jones, Nathan Robbins, Abdullah Alkhattabi, Mariah C Worley, Xu Gao, Valerie M Lasko-Roiniotis, Rajiv Karani, Logan Fulford, Min Jiang, Michelle Nieman, John N Lorenz, Jack Rubinstein
OBJECTIVE: Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. METHODS: We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps...
March 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/27991560/trpc3-gef-h1-axis-mediates-pressure-overload-induced-cardiac-fibrosis
#12
Takuro Numaga-Tomita, Naoyuki Kitajima, Takuya Kuroda, Akiyuki Nishimura, Kei Miyano, Satoshi Yasuda, Koichiro Kuwahara, Yoji Sato, Tomomi Ide, Lutz Birnbaumer, Hideki Sumimoto, Yasuo Mori, Motohiro Nishida
Structural cardiac remodeling, accompanying cytoskeletal reorganization of cardiac cells, is a major clinical outcome of diastolic heart failure. A highly local Ca(2+) influx across the plasma membrane has been suggested to code signals to induce Rho GTPase-mediated fibrosis, but it is obscure how the heart specifically decodes the local Ca(2+) influx as a cytoskeletal reorganizing signal under the conditions of the rhythmic Ca(2+) handling required for pump function. We found that an inhibition of transient receptor potential canonical 3 (TRPC3) channel activity exhibited resistance to Rho-mediated maladaptive fibrosis in pressure-overloaded mouse hearts...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884747/novel-function-of-%C3%AE-1d-l-type-calcium-channel-in-the-atria
#13
Ujala Srivastava, Ademuyiwa S Aromolaran, Frank Fabris, Deana Lazaro, John Kassotis, Yongxia Qu, Mohamed Boutjdir
Ca entry through atrial L-type Calcium channels (α1C and α1D) play an important role in muscular contraction, regulation of gene expression, and release of hormones including atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP). α1D Ca channel is exclusively expressed in atria, and has been shown to play a key role in the pathogenesis of atrial fibrillation. Recent data have shown that the small conductance calcium-activated potassium channel, SK4 is also atrial specific and also contributes prominently to the secretion of ANP and BNP...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27804106/the-role-of-transient-receptor-potential-vanilloid-2-channel-in-cardiac-aging
#14
Shannon Jones, Adrien Mann, Mariah C Worley, Logan Fulford, David Hall, Rajiv Karani, Min Jiang, Nathan Robbins, Jack Rubinstein, Sheryl E Koch
BACKGROUND: The aging heart is characterized by cellular and molecular changes leading to a decline in physiologic function and cardiac remodeling, specifically the development of myocyte hypertrophy and fibrosis. Transient receptor potential vanilloid 2 (TRPV2), a stretch-mediated channel and regulator of calcium homeostasis, plays a key role in the function and structure of the heart. TRPV2 also plays an important role in the adaptive and maladaptive compensatory mechanisms of the heart in response to pathologic and exercise-induced stress...
November 1, 2016: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/27618660/molecular-insights-into-the-mechanism-of-calmodulin-inhibition-of-the-eag1-potassium-channel
#15
Maria João Marques-Carvalho, Johannes Oppermann, Eva Muñoz, Andreia S Fernandes, Guillaume Gabant, Martine Cadene, Stefan H Heinemann, Roland Schönherr, João Henrique Morais-Cabral
The human EAG1 potassium channel belongs to the superfamily of KCNH voltage-gated potassium channels that have roles in cardiac repolarization and neuronal excitability. EAG1 is strongly inhibited by Ca(2+)/calmodulin (CaM) through a mechanism that is not understood. We determined the binding properties of CaM with each one of three previously identified binding sites (BDN, BDC1, and BDC2), analyzed binding to protein stretches that include more than one site, and determined the effect of neighboring globular domains on the binding properties...
October 4, 2016: Structure
https://www.readbyqxmd.com/read/27617892/cytokine-effects-on-mechano-induced-electrical-activity-in-atrial-myocardium
#16
REVIEW
V Kazanski, V M Mitrokhin, M I Mladenov, A G Kamkin
The role of cytokines as regulators of stretch-related mechanisms is of special importance since mechano-sensitivity plays an important role in a wide variety of biological processes. Here, we elucidate the influence of cytokine application on mechano-sensitivity and mechano-transduction. The atrial myocardial stretch induces production of interleukin (IL)-2, IL-6, IL-13, IL-17A, and IL-18 with exception of tumor necrosis factor α (TNF-α), IL-1β, and vascular endothelial growth factor B (VEGF-B). Positive ionotropic effect was specific for VEGF-B, negative ionotropic effects were specific for TNF-α, IL-1β, IL-2, IL-6, IL-13, IL-17A and IL-18, while IL-1α doesn't show direct ionotropic effect...
January 2017: Immunological Investigations
https://www.readbyqxmd.com/read/27573189/collagen-regulates-transforming-growth-factor-%C3%AE-receptors-of-hl-1-cardiomyocytes-through-activation-of-stretch-and-integrin-signaling
#17
Yen-Yu Lu, Yung-Kuo Lin, Yu-Hsun Kao, Cheng-Chih Chung, Yung-Hsin Yeh, Shih-Ann Chen, Yi-Jen Chen
The extracellular matrix (ECM) and transforming growth factor-β (TGF)-β are important in cardiac fibrosis, however, the effects of the ECM on TGF‑β signaling remain to be fully elucidated. The aims of the present study were to evaluate the role of collagen in TGF‑β signaling and examine the underlying mechanisms. In the present study, western blot analysis was used to examine TGF‑β signaling in HL‑1 cells treated with and without (control) type I collagen (10 µg/ml), which was co‑administered with either an anti‑β1 integrin antibody (10 µg/ml) or a stretch‑activated channel inhibitor (gadolinium; 50 µM)...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27545966/joint-influence-of-transmural-heterogeneities-and-wall-deformation-on-cardiac-bioelectrical-activity-a-simulation-study
#18
P Colli Franzone, L F Pavarino, S Scacchi
The aim of this work is to investigate, by means of numerical simulations, the influence of myocardial deformation due to muscle contraction and relaxation on the cardiac repolarization process in presence of transmural intrinsic action potential duration (APD) heterogeneities. The three-dimensional electromechanical model considered consists of the following four coupled components: the quasi-static transversely isotropic finite elasticity equations for the deformation of the cardiac tissue; the active tension model for the intracellular calcium dynamics and cross-bridge binding; the anisotropic Bidomain model for the electrical current flow through the deforming cardiac tissue; the membrane model of ventricular myocytes, including stretch-activated channels...
October 2016: Mathematical Biosciences
https://www.readbyqxmd.com/read/27220808/p2y2-purinergic-receptors-are-highly-expressed-in-cardiac-and-diaphragm-muscles-of-mdx-mice-and-their-expression-is-decreased-by-suramin
#19
Drielen De Oliveira Moreira, Humberto Santo Neto, Maria Julia Marques
INTRODUCTION: In Duchenne muscular dystrophy (DMD) and in the mdx mouse model of DMD, the lack of dystrophin leads to increased calcium influx and muscle necrosis. Patients suffer progressive muscle loss, and cardiomyopathy is an important determinant of morbidity. P2 purinergic receptors participate in the increased calcium levels in dystrophic skeletal muscles. METHODS: In this study, we evaluated whether P2 receptors are involved in cardiomyopathy in mdx mice at later stages of the disease...
January 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/27087858/increased-cell-membrane-capacitance-is-the-dominant-mechanism-of-stretch-dependent-conduction-slowing-in-the-rabbit-heart-a-computational-study
#20
Bernardo L de Oliveira, Emily R Pfeiffer, Joakim Sundnes, Samuel T Wall, Andrew D McCulloch
Volume loading of the cardiac ventricles is known to slow electrical conduction in the rabbit heart, but the mechanisms remain unclear. Previous experimental and modeling studies have investigated some of these mechanisms, including stretch-activated membrane currents, reduced gap junctional conductance, and altered cell membrane capacitance. In order to quantify the relative contributions of these mechanisms, we combined a monomain model of rabbit ventricular electrophysiology with a hyperelastic model of passive ventricular mechanics...
June 1, 2015: Cellular and Molecular Bioengineering
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