- MeSH
- Biological Transport physiology MeSH
- Research Support as Topic MeSH
- Homeostasis MeSH
- Rabbits MeSH
- Rats MeSH
- Myocardium MeSH
- Cell Membrane Permeability MeSH
- Sodium-Calcium Exchanger physiology MeSH
- Mammals MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Rats MeSH
- Animals MeSH
- Publication type
- Review MeSH
- Comparative Study MeSH
We aimed to determine the impact of Ca(2+)-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca(2+) handling. Langedorff-perfused rat or guinea pig hearts subjected to K(+)-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca(2+) disturbances and Ca(2+) overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca(2+)](i)-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca(2+)-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias.
- MeSH
- Potassium MeSH
- Homeostasis MeSH
- Myocytes, Cardiac metabolism ultrastructure MeSH
- Rats MeSH
- Guinea Pigs MeSH
- Norepinephrine MeSH
- Calcium Metabolism Disorders complications pathology MeSH
- Swine MeSH
- Arrhythmias, Cardiac etiology metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Guinea Pigs MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Cell Membrane MeSH
- Endoplasmic Reticulum MeSH
- Mitochondria MeSH
- Neurons MeSH
- Calcium MeSH
- Calcium Channels MeSH
- Publication type
- Review MeSH
We studied hsBAFF activity in in vitro mouse splenic B cells. hsBAFF effects on intracellular free Ca2+ concentration ([Ca2+]i) were assayed, using a laser scanning confocal microscope with fluorescent probe, Fluo-3/AM. We showed that treatment of B cells with 0.5-5 µg/ml hsBAFF resulted in significantly higher [Ca2+]i levels in a dose-dependent fashion at 12 and 24 h, respectively (p<0.05 or p<0.01 vs. control). Furthermore, we noticed that 2.5 µg/ml hsBAFF-treated cells were significantly resistant to decrease of cellular viability induced by thapsigargin (Tg), an endoplasmic reticulum (ER) Ca2+-ATPase inhibitor (p<0.05 hsBAFF plus Tg group vs. Tg group). Thus hsBAFF may promote B cell survival by direct upregulation of [Ca2+]i physiological homeostasis contributing to prevention of [Ca2+]i dysfunction. Using immunocytochemistry and Western blot analysis, we found that the activation of ERK1/2 due to hsBAFF was triggered by a [Ca2+]i-dependent pathway, leading to elevation of B cell proliferation. This is supported by the findings that intracellular Ca2+ chelator BAPTA/AM attenuated phosphorylated ERK1/2 expression and cell proliferation in hsBAFF-stimulated B cells. hsBAFF-stimulated B cell proliferation was obviously reduced by mitogen extracellular kinase 1/2 (MEK1/2, upstream of ERK1/2) inhibitor U0126. Taken together, the main finding of this study is that hsBAFF elicits higher but homeostatic [Ca2+]i levels, which regulates ERK1/2 activity and cell proliferation in in vitro B cells
- MeSH
- B-Lymphocytes enzymology MeSH
- Butadienes pharmacology MeSH
- Time Factors MeSH
- Chelating Agents pharmacology MeSH
- Egtazic Acid analogs & derivatives pharmacology MeSH
- B-Cell Activating Factor metabolism MeSH
- Financing, Organized MeSH
- Phosphorylation MeSH
- Homeostasis MeSH
- Enzyme Inhibitors pharmacology MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mitogen-Activated Protein Kinase 1 metabolism MeSH
- Mitogen-Activated Protein Kinase 3 metabolism MeSH
- Mice, Inbred ICR MeSH
- Mice MeSH
- Nitriles pharmacology MeSH
- Cell Proliferation MeSH
- Sarcoplasmic Reticulum Calcium-Transporting ATPases antagonists & inhibitors metabolism MeSH
- Thapsigargin pharmacology MeSH
- Calcium metabolism MeSH
- Cell Survival MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
The extracellular matrix (ECM) consists of proteins, glycosaminoglycans and glycoproteins, that support the dynamic interactions between cells, including intercellular communication, cell attachment, cell differentiation, cell growth and migration. As such, the ECM represents an essential and very sensitive system within the tissue microenvironment that is involved in processes such as tissue regeneration and carcinogenesis. The aim of the present review is to evaluate its diversity through Ca(2+) signaling and its role in muscle cell function. Here, we discuss some methodological approaches dissecting Ca(2+) handling mechanisms in myogenic and non-myogenic cells, e.g. the importance of Ca(2+) and calpains in muscle dystrophy. We also consider the reconstruction of skeletal muscle by colonization of decellularized ECM with muscle-derived cells isolated from skeletal muscle. Therefore, it is necessary to establish new methodological procedures based on Ca(2+) signaling in skeletal muscle cells and their effect on ECM homeostasis, allowing the monitoring of skeletal muscle reconstruction and organ repair.
- MeSH
- Extracellular Matrix metabolism MeSH
- Homeostasis physiology MeSH
- Intracellular Fluid metabolism MeSH
- Muscle, Skeletal metabolism MeSH
- Humans MeSH
- Calcium Signaling physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Koncentrácia voľného cytosolového vápnika ([Ca2+]i) je veľmi dôležitým signálnym mediátorom pre množstvo biologických systémov. Katióny vápnika (Ca2+) sú významnými ubikvitárnymi poslami, ktoré kontrolujú široké spektrum bunkových procesov. [Ca2+]i je kontrolovaná mechanizmami, ktoré regulujú vstup vápnika z extracelulárneho priestoru a jeho uvoľnenie z intracelulárnych priestorov. Aktivitou ATP-dependentných Ca2+ púmp a výmenníkových systémov sa vápnik vracia do intracelulárnych zásobníkov alebo sa odčerpáva z bunky. Chronické ochorenie obličiek je spojené so signifikantným zvýšením [Ca2+]i, ktoré je pre bunky toxické a môže byť zodpovedné za mnohé orgánové poruchy. Za zmeny vápnikovej homeostázy buniek u pacientov s chronickým ochorením obličiek zodpovedá navzájom prepojený komplex procesov. Naše štúdie objasňujú patofyziologické mechanizmy, podieľajúce sa na zmenenej homeostáze vápnika v periférnych mononukleárnych bunkách, ktoré sú modelom neexcitabilných buniek. [Ca2+]i je signifikantne zvýšená už v skorých štádiách chronického ochorenia obličiek. Koncentrácia intracelulárnych vápnikových rezerv a kapacitný vstup vápnika sú v porovnaní so zdravými dobrovoľníkmi významne zvýšené. Na tomto zvýšení sa podieľajú aj „pore-forming“ P2X7 receptory, ktoré majú u pacientov s chronickým ochorením obličiek zmenenú funkciu a vo zvýšenej miere sa exprimujú. Na druhej strane je aktivita plazmatických Ca2+-ATPáz zodpovedných za odstraňovanie nadbytočného vápnika z bunky znížená o 25 %. To znamená, že pri chronickom ochoreniu obličiek sú porušené ako mechanizmy vstupu, tak aj výstupu vápnika z bunky. Všetky tieto poruchy sa v signalizácii vápnika podieľajú na zvýšenej [Ca2+]i už v skorých štádiách renálneho ochorenia.
Free intracellular calcium represents a critical signaling mediator in a number of biological systems. Calcium cations (Ca2+) are an important ubiquitous messenger, controlling a broad range of cellular processes. Free cytosolic calcium concentration ([Ca2+]i) is controlled by mechanisms that regulate Ca2+ entry from the extracellular space and Ca2+ release from intracellular stores, and by the activity of ATP-dependent Ca2+ pumps and antiporters that move Ca2+ back into stores or out of cells. Chronic kidney disease is associated with a significant elevation in [Ca2+]i which is toxic to the cells and may be responsible for a multiple organ dysfunction. Disturbances in cellular calcium homeostasis in patients with chronic kidney disease represent a complex process. Our studies elucidate pathophysiological mechanisms of altered cellular calcium homeostasis in the peripheral blood mononuclear cells which represent the model of nonexcitable cells in patients with chronic kidney disease. The results demonstrate that [Ca2+]i is significantly increased in peripheral blood mononuclear cells already in early stages of chronic kidney disease. The calcium concentration of intracellular stores and the capacitative calcium entry into the cells of these patients are significantly higher in comparison with healthy volunteers. Also the pore-forming P2X7 receptors participate in increased [Ca2+]i in peripheral blood mononuclear cells of patients with chronic kidney disease. An altered P2X7 receptor function and increased P2X7 receptor expression may contribute to the complex disturbances in intracellular calcium homeostasis in chronic kidney disease. On the other hand, the activity of plasmatic membrane Ca2+-ATPases which is responsible for removing excessive calcium out of the cell, was found to be decreased by 25 % when compared to healthy subjects. It means that not only the mechanisms of entry, but also of the removal are impaired by the disease. All these alterations in calcium signaling are contributing very likely to the elevated [Ca2+]i from early stages of chronic kidney disease.
- MeSH
- Plasma Membrane Calcium-Transporting ATPases * diagnostic use metabolism deficiency MeSH
- Kidney Failure, Chronic * metabolism MeSH
- Child MeSH
- Adult MeSH
- Homeostasis physiology MeSH
- Intracellular Membranes metabolism MeSH
- Intracellular Space * metabolism MeSH
- Humans MeSH
- Calcium * metabolism MeSH
- Calcium Signaling * physiology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
Stem cells (SCs) of different origins have brought hope as potential tools for the treatment of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and Amyotrophic Lateral Sclerosis. Calcium signalling plays a key role in SC differentiation and proliferation, and dysregulation of Ca(2+) homeostasis may instigate pathological scenarios. Currently, the role of ion channels and receptors in SCs is not fully understood. In the recent years, we found that (i) the pre-differentiation of human embryonic SCs (hESCs) led to the activation of Ca(2+) signalling cascades and enhanced the functional activities of these cells, (ii) the Ca(2+) homeostasis and the physiological properties of hESC-derived neural precursors (NPs) changed during long term propagation in vitro, (iii) differentiation of NPs derived from human induced pluripotent SCs affects the expression of ion channels and receptors, (iv) these neuronal precursors exhibited spontaneous activity, indicating that their electrophysiological and Ca(2+) handling properties are similar to those of mature neurones, and (v) in mesenchymal SCs isolated from the adipose tissue and bone marrow of rats the expression profile of ion channels and receptors depends not only on the differentiation conditions but also on the source from which the cells were isolated, indicating that the fate and functional properties of the differentiated cells are driven by intrinsic mechanisms. Together, identification and assignment of a unique ion channel and a Ca(2+) handling footprint for each cell type would be necessary to qualify them as physiologically suitable for medical research, drug screening, and cell therapy.
- MeSH
- Cell Differentiation * MeSH
- Stem Cells cytology metabolism MeSH
- Humans MeSH
- Calcium metabolism MeSH
- Calcium Signaling * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
