The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects cardiac function development heart failure by regulating production second messenger cyclic adenosine monophosphate (cAMP). spatial localization in these betaARs, which are coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins), functional implications their have been unclear. We combined nanoscale live-cell scanning ion conductance fluorescence resonance energy...

Background Intrahepatic cholestasis of pregnancy (ICP) is a common disease affecting up to 5% pregnancies and which can cause fetal arrhythmia sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC), raised in the bloodstream ICP, acutely alter rate rhythm contraction induce abnormal calcium destabilization cultured neonatal rat cardiomyocytes (NRCM). Apart from their hepatic functions acids are ubiquitous signalling molecules with diverse systemic effects...

Intrahepatic cholestasis of pregnancy may be complicated by fetal arrhythmia, hypoxia, preterm labor, and, in severe cases, intrauterine death. The precise etiology death is not known. However, taurocholate has been demonstrated to cause arrhythmia and abnormal calcium dynamics cardiomyocytes. To identify the underlying reason for increased susceptibility cardiomyocytes we studied myofibroblasts (MFBs), which appear during structural remodeling adult diseased heart. In vitro , they...

Ca(2+)-induced Ca(2+) release (CICR) is critical for contraction in cardiomyocytes. The transverse (t)-tubule system guarantees the proximity of triggers [L-type channel, dihydropyridine receptors (DHPRs)] and sarcoplasmic reticulum channels [ryanodine (RyRs)]. Transverse tubule disruption occurs early heart failure (HF). Clinical studies left ventricular assist devices HF indicate that mechanical unloading induces reverse remodelling. We hypothesize failing hearts normalizes t-tubule...

Prolonged mechanical unloading (UN) of the heart is associated with detrimental changes to structure and function cardiomyocytes. The mechanisms underlying these are unknown. In this study, we report influence UN on excitation-contraction coupling, Ca(2+)-induced Ca(2+) release (CICR) in particular, transverse (t)-tubule structure. was induced male Lewis rat hearts by heterotopic abdominal transplantation. Left ventricular cardiomyocytes were isolated from transplanted after 4 wk studied...

The goal of this study was to examine the effect chronic heterogeneous shear stress, applied using an orbital shaker, on endothelial cell morphology and expression cyclooxygenases 1 2.Porcine aortic cells were plated fibronectin-coated Transwell plates. Cells cultured for up 7 days either under static conditions or shaker that generated a wave medium inducing stress over cells. fixed stained surface marker CD31 2. En face confocal microscopy scanning ion conductance used show randomly...

The transverse (t)-tubule system plays an essential role in healthy and diseased heart muscle, particularly Ca2+-induced Ca2+ release (CICR), its structural disruption is early event failure. Both mechanical overload unloading alter t-tubule structure, but the mechanisms mediating normally tight regulation of t-tubules response to load variation are poorly understood. Telethonin (Tcap) a stretch-sensitive Z-disc protein that binds proteins membrane. To assess regulating structure function,...

The review is devoted to Alexey Vereninov's research in the field of cell permeability and ion homeostasis. Particular attention paid modeling approach developed study frog striated muscles subsequently applied other types. Biologically relevant ways by which were studied model that was constructed determines overall nonreductionist research. In first excitability invertebrate tissues organs Vereninov used techniques methods derived from his teacher Dmitry Nasonov. From 1963 1971, he tested...

Staurosporine (STS) and etoposide (Eto) induced apoptosis of the human histiocytic lymphoma cells U937 were studied to determine role monovalent ions in apoptotic cell shrinkage. Cell shrinkage, defined as dehydration, was assayed by measurement buoyant density continuous Percoll gradient. The K+ Na+ content different fractions estimated flame emission analysis. Apoptosis evaluated confocal microscopy flow cytometry acridine orange stained cells, DNA effector caspase activity. 1 µM STS for 4...

The mechanism of apoptotic cell volume decrease was studied in rat thymocytes treated with dexamethasone (Dex) or etoposide (Eto). Cell shrinkage, i.e. dehydration, quantified by using buoyant density the a continuous Percoll gradient. K+ and Na+ content cells from different fractions were assayed flame emission analysis. Apoptosis tested microscopy flow cytometry acridine orange stained as well DNA cytometry. Treatment 1 µM Dex for 4-5.5 h 50 Eto 5 resulted appearance new distinct...

Embryonic stem cell-derived cardiomyocytes (ESC-CM) have many of the phenotypic properties authentic cardiomyocytes, and great interest has been shown in their possibilities for modelling human disease. Obstetric cholestasis affects 1 200 pregnant women United Kingdom. It is characterized by raised serum bile acids complicated premature delivery unexplained fetal death at late gestation. suggested that caused enhanced arrhythmogenic effect heart, neonatal susceptibility to acid-induced...

Aortic valve endothelial cells (ECs) function in vastly different levels of shear stress. The biomechanical characteristics on each side have not been investigated. We assessed the morphology and mechanical properties cultured or native ECs intact porcine aortic cusps using a scanning ion conductance microscope (SICM). autocrine influence several endothelial-derived mediators cell compliance expression actin were also examined. Cells are characterized by more elongated shape aligned along...

Abstract Unidirectional 22 Na, Li + and Rb fluxes net of Na K were measured in U937 human leukemic cells before after induction apoptosis by staurosporine (1 μM, 4 h) to answer the question which ion transporter(s) are responsible for changes cell water balance at apoptosis. The original version mathematical model was used analysis unidirectional under balanced distribution major monovalent ions across membrane. values all components efflux influx, i.e. via ,K ‐ATPase pump, channels, Na/Na...

Ouabain-sensitive (OS) and -resistant (OR) Rb(+) influx was examined in three sublines of U937 cells to compare alterations K(+) channel permeability the Na(+),K(+)-ATPase pump leading shift ion water balance during apoptosis induced by 0.2 1microM staurosporine (STS) for 4-5 h. Cell K(+), Rb(+), Na(+) Cl(-) content determined flame photometry (36)Cl distribution. Changes cell were monitored measurement buoyant density distribution [(3)H]-glycerol or 3-O-methyl-D-[(3)H]glucose. Apoptosis...

Background/Aims: Osmotic cell shrinkage is a powerful trigger of suicidal death or apoptosis, which paralleled and enforced by apoptotic volume decrease (AVD). Cells counteract regulatory increase (RVI). The present study explored the response human U937 cells to hypertonic solution thus elucidating relationship between RVI AVD. Methods: Cell water, concentration monovalent ions appearance markers were followed for 0.5-4 h after transferred medium. Intracellular K+, Na+, Cl– content,...

Recently, we have developed software that allows, using a minimum of required experimental data, to find the characteristics ion homeostasis and list all unidirectional fluxes monovalent ions through main pathways in cell membrane both balanced state during transient processes. Our approach has been successfully validated human proliferating lymphoid U937 cells processes after stopping Na/K pump by ouabain for staurosporine-induced apoptosis. In present study, used this erythrocytes resting...

Assessing the expression of channels on cell membrane is a necessary step in studying functioning ion living cells. We explore, first, if endogenous VRAC can be assayed using flow cytometry and commercially available antibody against an extracellular loop LRRC8A, also known as SWELL1, subunit channel. The second goal to determine increase number at responsible for chloride permeability two well-known cases: during staurosporine (STS)-induced apoptosis after water balance disturbance caused...

Background/aims Sodium is a key player in the fundamental cell functions. Fluorescent probes are indispensable tools for monitoring intracellular sodium levels single living cells. Since fluorescence of sodium-sensitive dyes cells significantly different from that an aqueous solution, signal calibrated situ indirectly using ionophores equalizing external and ion concentration. Attempts to compare data obtained fluorescent by direct flame emission analysis sparse results inaccurate. Methods...