stretch channels cardiac

BACKGROUND: . Many of the sensory receptors that encode touch, temperature, pain, and visual or auditory cues are well known. These exteroceptive receptors allow us to respond to external threats from the environment. The interoceptive sensory receptors that allow us to identify threats within the internal milieu, such as changes of our heart rate brought about by fright, gastric fullness with satiety, or breathing difficulty from increased respiratory resistance are not known. We postulated that the mechanosensitive piezo receptors in the heart are responsible for cardiac interoception in humans...

Endothelial surface glycocalyx (ESG) is a carbohydrate-rich layer found on the endothelial cell (EC) surface lining all blood vessels' inner lumen. Composed of membrane glycoproteins, glycosaminoglycans (GAGs), such as hyaluronan and heparan sulfate (HS), and proteoglycans, the ESG forms a bulky, gel-like layer serving critical functions in blood flow mechanotransduction, endothelial permeability maintenance, leukocyte adhesion, and inflammation control. ESG is known for sensing shear stress of blood flow and transducing the mechanical signal into nitric oxide (NO) production...

Elevation of intracellular Ca2+ concentration ([Ca2+]i) activates Ca2+/calmodulin-dependent kinases (CaMK) and promotes gene transcription. This signaling pathway is referred to as excitation–transcription (E-T) coupling. Although vascular myocytes can exhibit E-T coupling, the molecular mechanisms and physiological/pathological roles are unknown. Multiscale analysis spanning from single molecules to whole organisms has revealed essential steps in mouse vascular myocyte E-T coupling. Upon a depolarizing stimulus, Ca2+ influx through Cav1...

In this study, the cardiac electro-mechanical model in a deforming domain is taken with the addition of mechanical feedback and stretch-activated channel current coupled with the ten Tusscher human ventricular cell level model that results in a coupled PDE-ODE system. The existence and uniqueness of such a coupled system in a deforming domain is proved. At first, the existence of a solution is proved in the deformed domain. The local existence of the solution is proved using the regularization and the Faedo-Galerkin technique...

Mechano-electric feedbacks (MEFs), which model how mechanical stimuli are transduced into electrical signals, have received sparse investigation by considering electromechanical simulations in simplified scenarios. In this paper, we study the effects of different MEFs modeling choices for myocardial deformation and nonselective stretch-activated channels (SACs) in the monodomain equation. We perform numerical simulations during ventricular tachycardia (VT) by employing a biophysically detailed and anatomically accurate 3D electromechanical model for the left ventricle (LV) coupled with a 0D closed-loop model of the cardiocirculatory system...

Human ether-á-go-go-related gene (hERG) channels are key regulators of cardiac repolarization, neuronal excitability, and tumorigenesis. hERG channels contain N-terminal Per-Arnt-Sim (PAS) and C-terminal cyclic nucleotide-binding homology (CNBH) domains with many long-QT syndrome (LQTS)-causing mutations located at the interface between these domains. Despite the importance of PAS/CNBH domain interactions, little is known about their affinity. Here, we used the surface plasmon resonance (SPR) technique to investigate interactions between isolated PAS and CNBH domains and the effects of LQTS-causing mutations R20G, N33T and E58D, located at the PAS/CNBH domain interface, on these interactions...

The contraction-relaxation cycle of the heart is one of the most robust mechanical systems in the body that adapts rapidly to the body's needs by changing mechanical parameters. In many respects, we can consider the cardiac system as a complex machine and can use engineering approaches to describe its function. The classical physiology of the heart also focused on understanding function but the new molecular level tools in light microscopy and nanoengineering now enable a deeper understanding of the physiology...

INTRODUCTION: ICl,stretch have been reported to be involved in the development of atrial fibrillation, so we observed the changes of transcription and translation levels of ICl,stretch in isolated atrial myocardium of heart failure canine models. MATERIAL AND METHODS: In the control group (N = 10), five dogs were untreated and the other five received sham operation, while dogs in the heart failure group (N = 10) were implanted with cardiac pacemakers and underwent right ventricular pacing to induce heart failure...

The understanding of the electrophysiological mechanisms that underlie mechanosensitivity of the sinoatrial node (SAN), the primary pacemaker of the heart, has been evolving over the past century. The heart is constantly exposed to a dynamic mechanical environment; as such, the SAN has numerous canonical and emerging mechanosensitive ion channels and signaling pathways that govern its ability to respond to both fast (within second or on beat-to-beat manner) and slow (minutes) timescales. This review summarizes the effects of mechanical loading on the SAN activity and reviews putative candidates, including fast mechanoactivated channels (Piezo, TREK, and BK) and slow mechanoresponsive ion channels [including volume-regulated chloride channels and transient receptor potential (TRP)], as well as the components of mechanochemical signal transduction, which may contribute to SAN mechanosensitivity...

In response to stretch, cardiac tissue produces natriuretic peptides, which have been suggested to have beneficial effects in heart failure patients. In the present study, we explored the mechanism of stretch-induced brain natriuretic peptide (Nppb) expression in cardiac fibroblasts. Primary adult rat cardiac fibroblasts subjected to 4 h or 24 h of cyclic stretch (10% 1 Hz) showed a 6.6-fold or 3.2-fold ( p < 0.05) increased mRNA expression of Nppb, as well as induction of genes related to myofibroblast differentiation...

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Mechanical cues are crucial for vascular development and the proper differentiation of various cell types. Piezo1 and Piezo2 are mechanically activated cationic channels expressed in various cell types, especially in vascular smooth muscle and endothelial cells. It is present as a transmembrane homotrimeric complex, regulating calcium influx. Local blood flow associated shear stress, in addition to blood pressure associated cell membrane stretching are key Piezo channel activators. There is rising proof, showcasing Piezo channels significance in myocytes, cardiac fibroblast, vascular tone maintenance, atherosclerosis, hypertension, NO generation, and baroreceptor reflex...

Pathological left ventricular hypertrophy (LVH) occurs in response to pressure overload and remains the single most important clinical predictor of cardiac mortality. The molecular pathways in the induction of pressure overload LVH are potential targets for therapeutic intervention. Current treatments aim to remove the pressure overload stimulus for LVH, but do not completely reverse adverse cardiac remodelling. Although numerous molecular signalling steps in the induction of LVH have been identified, the initial step by which mechanical stretch associated with cardiac pressure overload is converted into a chemical signal that initiates hypertrophic signalling remains unresolved...

Aim: Effective antiarrhythmic treatment of atrial fibrillation (AF) constitutes a major challenge, in particular, when concomitant heart failure (HF) is present. HF-associated atrial arrhythmogenesis is distinctly characterized by prolonged atrial refractoriness. Small-conductance, calcium-activated K+ (KCa , SK, KCNN ) channels contribute to cardiac action potential repolarization and are implicated in AF susceptibility and therapy. The mechanistic impact of AF/HF-related triggers on atrial KCa channels is not known...

The sinoatrial node (SAN), the primary pacemaker of the heart, consists of a heterogeneous population of specialized cardiac myocytes that can spontaneously produce action potentials, generating the rhythm of the heart and coordinating heart contractions. Spontaneous beating can be observed from very early embryonic stage and under a series of genetic programing, the complex heterogeneous SAN cells are formed with specific biomarker proteins and generate robust automaticity. The SAN is capable to adjust its pacemaking rate in response to environmental and autonomic changes to regulate the heart's performance and maintain physiological needs of the body...

The mechanical environment of cardiac cells changes continuously and undergoes major alterations during diseases. Most cardiac diseases, including atrial fibrillation, are accompanied by fibrosis which can impair both electrical and mechanical function of the heart. A key characteristic of fibrotic tissue is excessive accumulation of extracellular matrix, leading to increased tissue stiffness. Cells are known to respond to changes in their mechanical environment, but the molecular mechanisms underlying this ability are incompletely understood...

Atrial fibrillation (AF) is associated with electrical remodeling, leading to cellular electrophysiological dysfunction and arrhythmia perpetuation. Emerging evidence suggests a key role for epigenetic mechanisms in the regulation of ion channel expression. Histone deacetylases (HDACs) control gene expression through deacetylation of histone proteins. We hypothesized that class I HDACs in complex with neuron-restrictive silencer factor (NRSF) determine atrial K+ channel expression. AF was characterized by reduced atrial HDAC2 mRNA levels and upregulation of NRSF in humans and in a pig model, with regional differences between right and left atrium...

The beating heart possesses the intrinsic ability to adapt cardiac output to changes in mechanical load. The century-old Frank-Starling law and Anrep effect have documented that stretching the heart during diastolic filling increases its contractile force. However, the molecular mechanotransduction mechanism and its impact on cardiac health and disease remain elusive. Here we show that the mechanically activated Piezo1 channel converts mechanical stretch of cardiomyocytes into Ca2+ and reactive oxygen species (ROS) signaling, which critically determines the mechanical activity of the heart...

The deformation of the heart tissue due to the contraction can modulate the excitation, a phenomenon referred to as mechano-electrical feedback (MEF), via stretch-activated channels (SACs). The effects of MEF on the electrophysiology at high pacing rates are shown to be proarrhythmic in general. However, more study needs to be done to elucidate the underlying mechanism. In this work, we investigate the effects of MEF on cardiac alternans, which is an alternation in the width of the action potential and that typically occurs when the heart is paced at high rates, using a biophysically detailed electromechanical model of cardiac tissue...

BACKGROUND: Atrial natriuretic peptide (ANP), which is released by the heart in response to acute cardiac stretch, possesses cardiac electrophysiological properties that include modulation of ion channel function and repolarization. However, data regarding whether ANP can directly modulate electrical instability or arrhythmias are largely lacking. OBJECTIVE: This study sought to determine whether ANP modifies onset or electrophysiological characteristics of ventricular fibrillation (VF) induced by severe hypokalemia in an isolated heart model...