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stretch channels cardiac

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
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
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
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
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
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
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
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
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
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
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
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
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
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
Tobias Glück, Peter Alter
Therapeutic implications of marine omega-3 highly unsaturated fatty acids (HUFA) in cardiovascular disease are still discussed controversially. Several clinical trials report divergent findings and thus leave ambiguity on the meaning of oral omega-3 therapy. Potential prognostic indications of HUFA treatment have been predominantly studied in coronary artery disease, sudden cardiac death, ventricular arrhythmias, atrial fibrillation and heart failure of various origin. It is suspected that increased ventricular wall stress is crucially involved in the prognosis of heart failure...
July 2016: Vascular Pharmacology
Jan-Christoph Edelmann, Lizzie Jones, Remi Peyronnet, Liang Lu, Peter Kohl, Ursula Ravens
Cells residing in the cardiac niche are constantly experiencing physical stimuli, including electrical pulses and cyclic mechanical stretch. These physical signals are known to influence a variety of cell functions, including the secretion of growth factors and extracellular matrix proteins by cardiac fibroblasts, calcium handling and contractility in cardiomyocytes, or stretch-activated ion channels in muscle and non-muscle cells of the cardiovascular system. Recent progress in cardiac tissue engineering suggests that controlled physical stimulation can lead to functional improvements in multicellular cardiac tissue constructs...
2016: Methods in Molecular Biology
Rémi Peyronnet, Jeanne M Nerbonne, Peter Kohl
Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret, and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, is exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intracardially and are, thus, maintained even in heart transplant recipients...
January 22, 2016: Circulation Research
E Aguettaz, J J Lopez, A Krzesiak, L Lipskaia, S Adnot, R J Hajjar, C Cognard, B Constantin, S Sebille
In Duchenne muscular dystrophy (DMD), deficiency of the cytoskeletal protein dystrophin leads to well-described defects in skeletal muscle but also to dilated cardiomyopathy (DCM). In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The dystrophin deficiency leads to membrane instability and a high stress-induced Ca(2+) influx due to dysregulation of sarcolemmal channels such as stretch-activated channels (SACs). In this work divalent cation entry has been explored in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different conditions: at rest and during the application of an axial stretch...
April 2016: Cell Calcium
Jipeng Maa, Lifang Yang, Yanyan Maa, Xiaowu Wang, Jun Ren, Jian Yang
Cardiovascular disease is still the most frequent cause of death in both developed and developing countries while metabolic syndrome and myocardial ischemia reperfusion (I/R) injury are the common risk factors responsible for the impaired cardiac function. Transient receptor potential (TRP) channels are non-selective cation channels and sense a broad range of stimuli from physical conditions such as stretch to chemicals including capsaicin. The diverse studies have revealed multifunctional roles of TRP channels in the physiological conditions and various diseases while some members of TRP channel superfamily are demonstrated to participate in the pathophysiology of cardiometabolic diseases and myocardial ischemia reperfusion injury...
October 18, 2015: Current Drug Targets
Joon-Chul Kim, Sun-Hee Woo
Atrial myocytes are exposed to shear stress during the cardiac cycle and haemodynamic disturbance. In response, they generate a longitudinally propagating global Ca(2+) wave. Here, we investigated the cellular mechanisms underlying the shear stress-mediated Ca(2+) wave, using two-dimensional confocal Ca(2+) imaging combined with a pressurized microflow system in single rat atrial myocytes. Shear stress of ∼16 dyn cm(-2) for 8 s induced ∼1.2 aperiodic longitudinal Ca(2+) waves (∼79 μm s(-1)) with a delay of 0...
December 1, 2015: Journal of Physiology
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