stretch channels

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...

Primary hemifacial spasm (pHFS) is due to a benign compression of the facial motor nerve by an offending vessel, leading to increased nerve excitability. Facial nerve hyperexcitability presents two different aspects. First, there is a spontaneous and ectopic generation of action potentials on the incriminated nerve and then this ectopic impulse can propagate and spread "laterally" from one facial nerve branch to another. This results in spontaneous and synkinetic spasms affecting one hemiface. Although the increase in excitability certainly concerns the nucleus of the facial motor nerve in the brainstem, it seems unlikely that the primary origin of this hyperexcitability and the associated phenomenon of lateral spreading strictly originate at the nuclear level...

Mechanical ventilation is an important tool for supporting critically ill patients but may also exert pathological forces on lung cells leading to Ventilator-Induced Lung Injury (VILI). We hypothesised that inhibition of the force-sensitive transient receptor potential vanilloid (TRPV4) ion channel may attenuate the negative effects of mechanical ventilation. Mechanical stretch increased intracellular Ca2+ influx and induced release of pro-inflammatory cytokines in lung epithelial cells that was partially blocked by about 30% with the selective TRPV4 inhibitor GSK2193874, but nearly completely blocked with the pan-calcium channel blocker ruthenium red, suggesting the involvement of more than one calcium channel in the response to mechanical stress...

Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to cyclic mechanical stretch (CMS), which evokes VSMC death, phenotypic switching, and migration, leading to aortic dissection. We have revealed that CMS of rat aortic smooth muscle cells (RASMCs) caused JNK- and p38-dependent cell death and that a calcium channel blocker, azelnidipine and an angiotensin II receptor antagonist, olmesartan decreased the phosphorylation of JNK and p38 and, subsequently, decreased cell death by CMS...

The coupled effects of mechanical loading and chemical attack can dramatically weaken the durability of a material. In this study, reactive force field molecular dynamics and the GCMC method were utilized to investigate the degradation mechanism for a deformed C-S-H gel subjected to water attack. In the elastic region of the stress-strain relation, no water molecules invaded the deformed C-S-H gel tensioned along the y-direction. On the other hand, in the failure stage, the tension loading stretched/broke the Si-O-Si bond, resulting in the distortion of the "dreierketten" silicate chain distribution and ordered zigzag sheets built by the calcium oxygen octahedron...

How we sense touch is fundamental for many physiological processes. However, the underlying mechanism and molecular identity for touch sensation are largely unknown. Here, we report on defective gentle-touch behavioral responses in brv1 loss-of-function Drosophila larvae. RNAi and Ca2+ imaging confirmed the involvement of Brv1 in sensing touch and demonstrated that Brv1 mediates the mechanotransduction of class III dendritic arborization neurons. Electrophysiological recordings further revealed that the expression of Brv1 protein in HEK293T cells gives rise to stretch-activated cation channels...

Although vibrational signalling is among the most ancient and common forms of communication, many fundamental aspects of this communication channel are still poorly understood. Here, we studied mechanisms underlying orientation towards the source of vibrational signals in the stink bug Nezara viridula (Hemiptera, Pentatomidae), where female vibrational song enables male to locate her on the bean plant. At the junction between the main stem and the leaf stalks, male placed his legs on different sides of the branching and orientation at the branching point was not random...

Ultrastable sensing characteristics of the ionic chemiresistor skin (ICS) that is designed by using an intrinsically stretchable thermoplastic polyurethane electrolyte as a volatile organic compound (VOC) sensing channel are described. The hierarchically assembled polymer electrolyte film is observed to be very uniform, transparent, and intrinsically stretchable. Systematic experimental and theoretical studies also reveal that artificial ions are evenly distributed in polyurethane matrix without microscale phase separation, which is essential for implementing high reliability of the ICS devices...

Imaging photoplethysmography (iPPG) is an emerging technology used to assess microcirculation and cardiovascular signs by collecting backscattered light from illuminated tissue using optical imaging sensors. The aim of this study was to study how effective smart garment fabrics could be capturing physiological signs in a non-contact mode. The present work demonstrates a feasible approach of, instead of using conventional high-power illumination sources, integrating a grid of surface-mounted light emitting diodes (LEDs) into cotton fabric to spotlight the region of interest (ROI)...

The mechanism of mechanosensitive gating of ion channels underlies many physiological processes, including the sensations of touch, hearing, and pain perception. TREK-2 is the best-studied mechanosensitive member of the two-pore domain potassium channel family. Apart from pressure sensing, it responds to a diverse range of stimuli. Two states, termed "up" and "down," are known from x-ray structural crystallographic studies and have been suggested to differ in conductance. However, the structural details of the gating behavior are largely unknown...

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...

Mechanosensitive channels are ubiquitous in bacteria and provide an essential mechanism to survive sudden exposure to a hypo-osmotic environment by sensing and release of increased turgor pressure. No mechanosensitive channels have thus far been identified and characterized for the human-specific bacterial pathogen Neisseria gonorrhoeae In this study, we identified and characterized the N. gonorrhoeae MscS-like mechanosensitive channel (Ng-MscS). Electrophysiological analyses by patch-clamp showed that Ng-MscS is stretch-activated and contains pressure-dependent gating properties...

Quiescence of myometrium contractile activity allows uterine expansion to accommodate the growing fetus and prevents preterm labor particularly during excessive uterine stretch in multiple pregnancy. However, the mechanisms regulating uterine response to stretch are unclear. We tested the hypothesis that prolonged uterine stretch is associated with decreased myometrium contractile activity via activation of TWIK-related K+ channel (TREK-1). Pregnant women at different gestational age (preterm and term) and uterine stretch (singleton and twin pregnancy) were studied, and uterine strips were isolated for measurement of contractile activity and TREK-1 channel expression/activity...

Photoprotection is fundamental in photosynthesis to avoid oxidative photodamage upon excess light exposure. Excited chlorophylls (Chl) are quenched by carotenoids, but the precise molecular origin remains controversial. The cyanobacterial HliC protein belongs to the Hlip family ancestral to plant light-harvesting complexes, and binds Chl a and β-carotene in 2:1 ratio. We analyzed HliC by watermarked femtosecond stimulated Raman spectroscopy to follow the time evolution of its vibrational modes. We observed a 2 ps rise of the C═C stretch band of the 2Ag - (S1 ) state of β-carotene upon Chl a excitation, demonstrating energy transfer quenching and fast excess-energy dissipation...

AIMS: To investigate the localization of phosphodiesterase 5 (PDE5) and the molecular mechanism underlying the effect of the PDE5 inhibitor tadalafil in signal transduction in the bladder urothelium. METHODS: PDE5 expression in rat bladder tissues and cultured primary rat bladder urothelial cells was evaluated using immunochemistry and western blot assays. Ca2+ influx in cells exposed to isotonic solution, hypotonic solution, a selective transient receptor potential vanilloid 2 (TRPV2) channel agonist (cannabidiol), a selective TRPV4 channel agonist (GSK1016790A), a TRP cation channel melastatin 7 (TRPM7) channel agonist (PIP2), or a purinergic receptor agonist (ATP) in the presence or absence of 10 µM tadalafil was evaluated using calcium imaging techniques...

. The role of aqueous surfaces in promoting atmospheric chemistry is increasingly being recognized. However, the bimolecular chemistries of Criegee intermediates, which influence the tropospheric budget of OH radicals, organic acids, hydroperoxides, nitrates, sulfates and particulate material, remain less explored on an aqueous surface. Herein we have employed Born Oppenheimer molecular dynamics simulations and two-layer ONIOM(QM:MM) in electronic embedding scheme to study the reaction and the spectroscopic signal of anti-CH3CHOO with nitric acid (HNO3) at the air-water interface, which is expected to be an important reaction in the polluted urban environments...

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...

Ca2+ impacts a large array of cellular processes in every known cell type. In the white adipocyte, Ca2+ is involved in regulation of metabolic processes such as lipolysis, glucose uptake and hormone secretion. Although the importance of Ca2+ in control of white adipocyte function is clear, knowledge is still lacking regarding the control of dynamic Ca2+ alterations within adipocytes and mechanisms inducing intracellular Ca2+ changes remain elusive. Own work has recently demonstrated the existence of store-operated Ca2+ entry (SOCE) in lipid filled adipocytes...

Odontoblasts, with their strategic arrangement along the outermost compartment of the dentin-pulp complex, have been suggested to have sensory function. In addition to their primary role in dentin formation, growing evidence shows that odontoblasts are capable of sensing mechanical stimulation. Previously, we found that most odontoblasts express TRPM7, the nonselective mechanosensitive ion channel reported to be critical in Mg2+ homeostasis and dentin mineralization. In line with this finding, we sought to elucidate the functional expression of TRPM7 in odontoblasts by pharmacological approaches and mechanical stimulation...

Astrocytic ATP release is essential for brain functions such as synaptic long-term potentiation for learning and memory. However, whether/how ATP is released via exocytosis remains hotly debated. All previous studies of non-vesicular ATP release have used indirect assays. In contrast, two recent papers report vesicular ATP release using more direct assays. In the present work, by using patch-clamped "ATP-sniffer-cells", we re-investigated astrocytic ATP release at single-vesicle resolution in hippocampal astrocytes...