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Results for “Calcium Signaling”

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At least 721 records · Page 40Linked to original sources
PubMed2000

Redox regulation of cardiac muscle calcium signaling.

Signal transduction for cardiac muscle contraction is regulated by the Ca2+-induced Ca2+-release mechanism. Redox reactions by biological oxidants and antioxidants have been shown to alter the kinetics of Ca2+-induced Ca2+ release. We postulate that altered kinetics of Ca2+-induced Ca2+ release may divert the contractile pool of Ca2+ to elicit excitation-transcription coupling. We provide evidence that redox reactions regulate excitation-transcription coupling by showing that membrane depolarization may activate the GATA4 transcription factor only when the cells are pretreated with hydrogen peroxide. Therefore, redox regulation of the ryanodine receptor may serve as a mechanism to determine whether the contractile pool of Ca2+ should signal gene transcription during excitation-contraction coupling.

Action Potentials↗
PubMed2004

Two-photon analysis of calcium signals in T lymphocytes of intact lamina propria from human intestine.

Lamina propria (LP) T cells of the human intestinal mucosa usually do not develop systemic immune responses despite permanent exposure to foreign antigens. The mechanisms maintaining this hyporeactivity in the normal gut are poorly understood. It is, at present, not clear what role the microenvironment of the mucosa plays for low T cell reactivity and in the pathogenesis of mucosal inflammation. Despite the importance of cytosolic Ca(2+) signals for T lymphocyte activation, intracellular Ca(2+) concentration measurements have so far only been performed in dissociated T cells, following disruption of the microenvironment. We used two-photon technology to measure Ca(2+) signals in identified T lymphocytes within the intact mucosa to minimize impact on tissue integrity while preserving the cellular microenvironment. We show that Ca(2+) signals in LP T cells correlate with the hyporeactivity of T cells in the intestinal immune system and furthermore link Ca(2+) signals with inflammatory bowel disease. Our data implicate that Ca(2+) signals in LP T cells do not depend on the microenvironment of the intact mucosa, since they are very similar to Ca(2+) signals in dissociated LP T cells.

Calcium↗
PubMed2005

Stimulation of group I metabotropic glutamate receptors evokes calcium signals and c-jun and c-fos gene expression in human T cells.

To study if the activation of group I mGlu receptors in human T cells modifies intracellular Ca2+ concentration ([Ca2+](i)) and cell function, we measured [Ca2+](i) on cell suspensions (spectrofluorimetric method) or single cell (digital Ca2+ imaging system) using fura-2 as indicator. Early-inducible gene (c-jun and c-fos) expression was studied by reverse transcriptase-polymerase chain reaction assay as representative of Ca(2+)-sensitive gene expression. (1S,3R)-ACPD (100 microM), the selective mGlu receptor agonist, evoked a significant increase (34.1+/-4.9%) of [Ca2+](i), pharmacologically characterized as mediated by group I mGlu receptors, since both (S)-3,5-DHPG (100 microM), a selective group I mGlu receptor agonist and CHPG (1mM), the specific mGlu5 receptor agonist, reproduced the effects, that were abolished by AIDA (1mM), a selective group I mGlu receptor antagonist. (S)-3,5-DHPG-induced a rapid [Ca2+](i) rise (initial phase) followed by a slow decrease (second phase) to the baseline. Both extracellular Ca2+ and Ca2+ released from intracellular stores contribute to the [Ca2+](i) increase which depend on PLC activation. In a Ca(2+)-free buffer, the second phase rapidly return to the baseline; LaCl3 (1-10 microM), an inhibitor of extracellular Ca2+ influx, significantly reduced the second phase only; thapsigargin (1microM), by discharging intracellular Ca2+ stores, U 73122 (10 microM) and D609 (300 microM), by inhibiting PLC activity, prevented both phases. In our system, PTX pre-treatment increased (S)-3,5-DHPG effects, demonstrating that PXT-sensitive G(i/o) proteins are involved. Finally, specific stimulation of these receptors in Jurkat cells upregulates c-jun and c-fos gene expression, thus activating multiple downstream signalling regulating important T cell functions.

Calcium Signaling↗
PubMed1989

[The calcium signal in the physiology of the secretory process. II. The effect of extracellular and intracellular calcium on secretory mechanisms].

Investigations of the influence of the extra- and intracellular calcium source on secretory processes helps the understanding of the physiology and pathophysiology of secretion. The ratio of the two calcium sources in the activation of secretion depends on the type of secretory cell, on the character of the secretagogue stimulus and the phase of the secretory process. The use of intracellular sources of calcium in the early stage of secretion explains the lack of an inhibitory action of calcium current blockers on the function of some hormonal systems in short-term studies, e.g. the tyrotropic and somatotropic system, or on adrenocortical secretion. Conversely inhibition of some hormonal functions in the curse of prolonged inhibition of calcium currents indicates the importance of the inflow of calcium ions from the extracellular space into the cytosol during long-term regulation of secretion. The author gives an account of the results of investigations which by means of calcium ionophores or calcium current antagonists provide evidence of the importance of an extracellular calcium source in the control of secretion of some systems.

Animals↗
PubMed2004

Modulation of cytosolic calcium signaling by protein kinase A-mediated phosphorylation of inositol 1,4,5-trisphosphate receptors.

Calcium release via intracellular Ca2+ release channels is a central event underpinning the generation of numerous, often divergent physiological processes. In electrically non-excitable cells, this Ca2+ release is brought about primarily through activation of inositol 1,4,5-trisphosphate receptors and typically takes the form of calcium oscillations. It is widely believed that information is carried in the temporal and spatial characteristics of these signals. Furthermore, stimulation of individual cells with different agonists can generate Ca2+ oscillations with dramatically different spatial and temporal characteristics. Thus, mechanisms must exist for the acute regulation of Ca2+ release such that agonist-specific Ca2+ signals can be generated. One such mechanism by which Ca2+ signals can be modulated is through simultaneous activation of multiple second messenger pathways. For example, activation of both the InsP3 and cAMP pathways leads to the modulation of Ca2+ release through protein kinase A mediated phosphoregulation of the InsP3R. Indeed, each InsP3R subtype is a potential substrate for PKA, although the functional consequences of this phosphorylation are not clear. This review will focus on recent advances in our understanding of phosphoregulation of InsP3R, as well as the functional consequences of this modulation in terms of eliciting specific cellular events.

Animals↗
PubMed1999

Regulation of human eosinophil migration across lung epithelial monolayers by distinct calcium signaling mechanisms in the two cell types.

In asthmatic patients, eosinophils massively infiltrate the lung tissues and migrate through lung epithelium into the airways. The regulatory mechanisms involved are obscure. We studied the role of calcium in the migration of human eosinophils across monolayers of human lung epithelial H292 cell line cells induced by combined chemotactic solutions of platelet-activating factor and C5a. The transepithelial migration of eosinophils was attenuated by depletion of the external Ca2+ in the migration system, whereas the eosinophil migration itself was unaffected as evidenced by measuring eosinophil chemotaxis in the Boyden chamber in the absence of epithelial cells. Buffering of intracellular Ca2+ in eosinophils with 1, 2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA/AM) inhibited both eosinophil transepithelial migration and eosinophil chemotaxis in the Boyden chamber, suggesting the importance of intracellular Ca2+ in eosinophil transmigration. Although loading of BAPTA/AM or addition of thapsigargin to the epithelial cells effectively changed their cytoplasmic free Ca2+ concentrations, neither of these treatments affected transepithelial migration of eosinophils. Interestingly, addition of La3+ (0.2 mM) to epithelial cells suppressed eosinophil transmigration whereas addition of La3+ to eosinophils did not. Taken together, these results show the importance of Ca2+ in eosinophil migration across lung epithelium and support a distinctive regulatory role of intracellular and extracellular Ca2+ for the two cell types involved in this process; i.e., the transmigration of human eosinophils across a monolayer of lung epithelial cells is regulated by the intracellular Ca2+ in eosinophils, whereas the ability of the lung epithelial cell monolayer to allow eosinophil passage is dependent on the extracellular Ca2+.

Buffers↗
PubMed1988

The calcium signal for BALB/MK keratinocyte terminal differentiation counteracts epidermal growth factor (EGF) very early in the EGF-induced proliferative pathway.

BALB/MK mouse epidermal keratinocytes require epidermal growth factor (EGF) for proliferation and terminally differentiate in response to high calcium concentrations. We show that EGF is an extremely potent mitogen, causing BALB/MK cultures to enter the cell cycle in a synchronous manner associated with a greater than 100-fold increase in DNA synthesis. Analysis of the expression of proto-oncogenes which have been reported to be activated during the cascade of events following growth factor stimulation of fibroblasts or lymphoid cells revealed a very rapid but transient 100-fold increase in c-fos RNA but little or no effect on the other proto-oncogenes analyzed. Exposure of EGF-synchronized BALB/MK cells to high levels of calcium was associated with a striking decrease in the early burst of c-fos RNA as well as the subsequent peak of cell DNA synthesis. Since the inhibitory effect of high calcium on c-fos RNA expression was measurable within 30 min, our studies imply that the EGF proliferative and calcium differentiation signals must interact very early in the pathway of EGF-induced proliferation. Our results also establish that c-fos RNA modulation is an important early marker of cell proliferation in epithelial as well as mesenchymal cells.

Animals↗
PubMed1996

Expression of purinergic receptor channels and their role in calcium signaling and hormone release in pituitary gonadotrophs. Integration of P2 channels in plasma membrane- and endoplasmic reticulum-derived calcium oscillations.

The role of ATP as a positive feedback element in Ca2+ signaling and secretion was examined in female rat pituitary gonadotrophs. ATP and ADP, but not AMP or adenosine, induced a dose- and extracellular Ca2+-dependent rise in [Ca2+]i in identified gonadotrophs in a Mg2+- and suramin-sensitive manner. ATP, adenosine-5'-O-(3-thiotriphosphate), adenosine-5'-O-(1-thiotriphosphate), 2-methylthio-ATP, and 3'-O-(4-benzoyl)benzoyl-ATP were roughly equipotent in rising [Ca2+]i in gonadotrophs, while ADP was effective only at submillimolar concentration range, and none of these compounds permeabilized the cells. On the other hand, alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, and UTP were unable to induce any rise in [Ca2+]i. This pharmacological profile is consistent with expression of P2X2 and/or P2X5 purinergic receptor channels. Patch-clamp experiments showed that ATP induced an inward depolarizing current in gonadotrophs clamped at -90 mV, associated with an increase in [Ca2+]i. The ATP-induced [Ca2+]i response was partially inhibited by nifedipine, a blocker of voltage-sensitive Ca2+ channels (VSCC), but was not affected by tetrodotoxin, a blocker of voltage-sensitive Na+ channels. Thus, the P2-depolarizing current itself drives Ca2+ into the cell, but also activates Ca2+ entry through VSCC. In accord with this, low [ATP] induced plasma membrane-dependent [Ca2+]i oscillations in quiescent cells, and increased the frequency of spiking in spontaneously active cells. ATP-induced Ca2+ influx also affected agonist-induced and InsP3-dependent [Ca2+]i oscillations by increasing the frequency, base line, and duration of Ca2+ spiking. In addition, ATP stimulated gonadotropin secretion and enhanced agonist-induced gonadotropin release. ATP was found to be secreted by pituitary cells during agonist stimulation and was promptly degraded by ectonucleotidase to adenosine. These observations indicate that ATP represents a paracrine/autocrine factor in the regulation of Ca2+ signaling and secretion in gonadotrophs, and that these actions are mediated by P2 receptor channels.

Adenosine Triphosphate↗
PubMed1996

Calcium signalling: sphingosine kinase versus phospholipase C?

A recent study shows that sphingosine kinase and its lipid product have an essential signalling function; they act in the mobilization of calcium ions in antigen-stimulated mast cells. This finding may have relevance to signalling in other cells of the immune system.

Animals↗
PubMed2006

Calcium signaling and exocytosis in adrenal chromaffin cells.

At a given cytosolic domain of a chromaffin cell, the rate and amplitude of the Ca2+ concentration ([Ca2+]c) depends on at least four efficient regulatory systems: 1) plasmalemmal calcium channels, 2) endoplasmic reticulum, 3) mitochondria, and 4) chromaffin vesicles. Different mammalian species express different levels of the L, N, P/Q, and R subtypes of high-voltage-activated calcium channels; in bovine and humans, P/Q channels predominate, whereas in felines and murine species, L-type channels predominate. The calcium channels in chromaffin cells are regulated by G proteins coupled to purinergic and opiate receptors, as well as by voltage and the local changes of [Ca2+]c. Chromaffin cells have been particularly useful in studying calcium channel current autoregulation by materials coreleased with catecholamines, such as ATP and opiates. Depending on the preparation (cultured cells, adrenal slices) and the stimulation pattern (action potentials, depolarizing pulses, high K+, acetylcholine), the role of each calcium channel in controlling catecholamine release can change drastically. Targeted aequorin and confocal microscopy shows that Ca2+ entry through calcium channels can refill the endoplasmic reticulum (ER) to nearly millimolar concentrations, and causes the release of Ca2+ (CICR). Depending on its degree of filling, the ER may act as a sink or source of Ca2+ that modulates catecholamine release. Targeted aequorins with different Ca2+ affinities show that mitochondria undergo surprisingly rapid millimolar Ca2+ transients, upon stimulation of chromaffin cells with ACh, high K+, or caffeine. Physiological stimuli generate [Ca2+]c microdomains in which the local subplasmalemmal [Ca2+]c rises abruptly from 0.1 to approximately 50 microM, triggering CICR, mitochondrial Ca2+ uptake, and exocytosis at nearby secretory active sites. The fact that protonophores abolish mitochondrial Ca2+ uptake, and increase catecholamine release three- to fivefold, support the earlier observation. This increase is probably due to acceleration of vesicle transport from a reserve pool to a ready-release vesicle pool; this transport might be controlled by Ca2+ redistribution to the cytoskeleton, through CICR, and/or mitochondrial Ca2+ release. We propose that chromaffin cells have developed functional triads that are formed by calcium channels, the ER, and the mitochondria and locally control the [Ca2+]c that regulate the early and late steps of exocytosis.

Adrenal Glands↗
PubMed2003

Calcium signalling during embryonic development.

Consider a hypothetical design specification for an integrated communication-control system within an embryo. It would require short-range (subcellular) and long-range (pan-embryonic) abilities, it would have to be flexible and, at the same time, robust enough to operate in a dynamically changing environment without information being lost or misinterpreted. Although many signalling elements appear, disappear and sometimes reappear during development, it is becoming clear that embryos also depend on a ubiquitous, persistent and highly versatile signalling system that is based around a single messenger, Ca2+.

Animals↗
PubMed2005

Intracellular cAMP and calcium signaling by serotonin in mouse cumulus-oocyte complexes.

cAMP and intracellular Ca2+ are important second messengers involved in mammalian follicular growth and oocyte meiotic maturation. We investigated the capacity of the neurohormone serotonin (5-hydroxytryptamine, 5-HT) to regulate intracellular cAMP and Ca2+ in mouse oocytes and surrounding cumulus cells. On the basis of a reverse transcription-polymerase chain reaction study, 5-HT7 receptor mRNA is expressed in cumulus cells, oocytes, and embryos up to the four-cell stage, and 5-HT2A and 5-HT2B receptor mRNAs are expressed in cumulus cells only, whereas 5-HT2C, 5-HT4, and 5-HT6 receptors are expressed in neither oocytes nor cumulus cells. The addition of 5-HT (10 nM to 10 microM) to isolated metaphase II oocytes had no effect on their internal cAMP or Ca2+ levels, whereas it caused dose-dependent cAMP and Ca2+ increases in cumulus cells. This cAMP increase in cumulus cells could be mimicked by 5-HT agonists with the following order of potency: 5-HT > 8-hydroxy-2-(di-n-propylamino) tetralin = alpha-methyl-5-HT = 5-carboxamidotryptamine maleate > 2-[1-(4-piperonyl)piperazinyl]benzo-triazole, thereby supporting a preferential involvement of 5-HT7 receptors. As measured with cumulus cells preloaded with fura-2/acetoxymethyl ester (AM), the addition of 5-HT also caused dose-dependent Ca2+ increases, which were probably linked to detected 5-HT2A and 5-HT2B receptors. Adding the Ca2+ ionophore ionomycin to cumulus cells resulted in both Ca2+ and cAMP elevations, whereas preincubation of cells with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM abolished the 5-HT-induced Ca2+ increase and reduced the cAMP increase, indicating cross-talk between the 5-HT-sensitive Ca2+ and cAMP pathways. Our results show that 5-HT may be a local regulator in mouse cumulus-oocyte complexes through its actions on cAMP and Ca2+ signaling, as mediated by 5-HT2A, 5-HT2B, and 5-HT7 receptors.

Animals↗
PubMed2003

IgE alone-induced actin assembly modifies calcium signaling and degranulation in RBL-2H3 mast cells.

In the mast cell signaling pathways, the binding of immunoglobulin E (IgE) to FcepsilonRI, its high-affinity receptor, is generally thought to be a passive step. In this study, we examined the effect of IgE alone, that is, without antigen stimulation, on the degranulation in mast cells. Monomeric IgE (500-5,000 ng/ml) alone increased cytosolic Ca2+ level ([Ca2+]i) and induced degranulation in rat basophilic leukemia (RBL)-2H3 mast cells. Monomeric IgE (5,000 ng/ml) alone also increased [Ca2+]i and induced degranulation in bone marrow-derived mast cells. Interestingly, monomeric IgE (5-50 ng/ml) alone, in concentrations too low to induce degranulation, increased filamentous actin content in RBL-2H3 mast cells. We next examined whether actin dynamics affect the IgE alone-induced RBL-2H3 mast cell activation pathways. Cytochalasin D inhibited the ability of IgE alone (50 ng/ml) to induce de novo actin assembly. In cytochalasin D-treated cells, IgE (50 ng/ml) alone increased [Ca2+]i and induced degranulation. We have summarized the current findings into two points. First, IgE alone increases [Ca2+]i and induces degranulation in mast cells. Second, IgE, at concentrations too low to increase either [Ca2+]i or degranulation, significantly induces actin assembly, which serves as a negative feedback control in the mast cell Ca2+ signaling and degranulation.

Actins↗
PubMed2004

Cutting edge: optical microspectrophotometry supports the existence of gel phase lipid rafts at the lamellipodium of neutrophils: apparent role in calcium signaling.

Although much progress has been made in elucidating the biochemical properties of lipid rafts, there has been less success in identifying these structures within living cell membranes, which has led to some concern regarding their existence. One difficulty in analyzing lipid rafts using optical microscopy is their small size. We now test the existence of lipid rafts in polarized neutrophils, which redistribute lipid raft markers into comparatively large lamellipodia. Optical microspectrophotometry of Laurdan-labeled neutrophils revealed a large blue shift at lamellipodia relative to cell bodies. This blue shift disappeared after exposure to methyl-beta-cyclodextrin (m beta CD), which disrupts lipid rafts. The Ca(2+) channel transient receptor potential-like channel-1, a lipid raft marker, traffics to lamellipodia, but redistributes uniformly about cells after exposure to m beta CD. This is accompanied by disruption of Ca(2+) waves normally initiated at lamellipodia. Thus, m beta CD-sensitive lipid-ordered domains are present at and participate in signaling from the lamellipodia of living neutrophils.

Biomarkers↗