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At least 775 records · Page 43Linked to original sources
PubMed2004

Extracellular ATP-induced calcium signaling in mIMCD-3 cells requires both P2X and P2Y purinoceptors.

Kidney tubules are targets for the activation of locally released nucleotides through multiple P2 receptor types. Activation of these P2 receptors modulates cellular Ca(2+) signaling and downstream cellular function. The purpose of this study was to determine whether P2 receptors were present in mIMCD-3 cells, a mouse inner medullary collecting duct cell line, and if so, to examine their link with intracellular Ca(2+) homeostasis. To monitor intracellular Ca(2+) concentration ([Ca(2+)](i)), experiments were conducted using the fluorescent dye fura 2. ATP (0.1-100 microM) produced a dose-dependent increase in [Ca(2+)](i) in a physiological Ca(2+)-containing solution, with an EC(50) of 2.5 microM. The P2-receptor antagonist PPADS reduced the effect of ATP on [Ca(2+)](i), and the P1-receptor agonist adenosine caused only a small increase in [Ca(2+)](i). Preincubation of cells with the phospholipase C antagonist U-73122 blocked the ATP-induced increase in [Ca(2+)](i), indicating P2Y receptors were involved in this process. In a Ca(2+)-free bath solution, thapsigargin and ATP induced intracellular Ca(2+) release from an identical pool. Nucleotides caused an increase in [Ca(2+)](i) in the potency order of UTP = ATP > ATP gamma S > ADP > UDP that is best fitted with the P2Y(2) subtype profile. Although the P2Y agonist UTP induced a similar large transient increase in [Ca(2+)](i) as did ATP, a small but sustained increase in [Ca(2+)](i) occurred only in ATP-stimulated cells, suggesting the role of P2X receptors in Ca(2+) influx. The sustained increase in [Ca(2+)](i) could be blocked by either nonselective cation channel blockers Gd(3+) or P2X antagonists PPADS and PPNDS. Furthermore, when either Gd(3+) or PPNDS was applied to the bath solution before ATP application, the ATP-induced increase in [Ca(2+)](i) was significantly reduced. Both RT-PCR and Western blotting corroborated the presence of P2X(1) and P2Y(2) receptors. These studies demonstrate that mIMCD-3 cells have both P2X and P2Y subtype receptors and that the activation of both P2X and P2Y receptors by extracellular ATP appears to be required to regulate intracellular Ca(2+) signaling.

Adenosine Triphosphate↗
PubMed2000

Calcium signaling and c-Fos gene expression via M3 muscarinic acetylcholine receptors in human T- and B-cells.

We previously showed that blood acetylcholine (ACh) originates mainly from T-lymphocytes, and that stimulation of muscarinic ACh receptors (mAChRs) induces Ca2+ oscillations and up-regulates c-fos gene expression in both T- and B-lymphocytes. In the present study, we investigated which mAChR subtypes are involved in Ca2+ signaling and c-fos gene expression in human T- (CEM) and B- (Daudi) cells. Stimulation of mAChRs with 100 microM oxotremorine-M, an M1/M3 agonist, increased levels of intracellular free Ca2+ ([Ca2+]i) and c-fos mRNA expression in both cell lines. 4-DAMP, an M3 antagonist, more effectively blocked the oxotremorine-M-induced increase in [Ca2+]i than pirenzepine and telenzepine, M1-receptor antagonists; AF-DX 116, an M2 antagonist; hexahydrosiladifenidol, a weak M3 antagonist; or hexamethonium and d-tubocurarine, nicotinic receptor antagonists. McN-A-343 (100 microM), a partial M1-receptor agonist, had no apparent effect on [Ca2+]i in either cell line. The oxotremorine-M-induced up-regulation of c-fos transcription was inhibited by 4-DAMP, but not by pirenzepine or AF-DX 116. Our findings thus suggest that ACh released from T-lymphocytes acts as an autocrine/paracrine factor, transmitting a Ca2+-dependent signal to the nuclei of T- and B-lymphocytes via M3 receptors.

Analysis of Variance↗
PubMed1997

Fc receptor-mediated phagocytosis, superoxide production and calcium signaling of beta 2 integrin-deficient bovine neutrophils.

Fc receptor for immunoglobulin G-mediated phagocytosis, superoxide production and intracellular calcium ([Ca2+]i) signaling of complement receptor type 3 (CR3)-deficient neutrophils from a heifer with leukocyte adhesion deficiency (BLAD) were compared to those of control heifers. The mean phagocytic activity of IgG-coated yeasts and aggregated bovine IgG (Agg-IgG)-induced superoxide production of CR3-deficient neutrophils were 10% and 77.9%, respectively, of those of control neutrophils. The [Ca2+]i signals in CR3-deficient neutrophils stimulated with Agg-IgG or concanavalin A were different with mean peak [Ca2+]i concentrations of 78% and 41.9%, respectively, of those of control neutrophils. These findings suggest that Fc receptor-mediated neutrophil functions are closely dependent on the presence of CR3 (CD11b/CD18) on the neutrophil cell surfaces.

Animals↗
PubMed1999

Polycations induce calcium signaling in glomerular podocytes.

BACKGROUND: The neutralization of the polyanionic surface of the podocyte by perfusion of kidneys with polycations, such as protamine sulfate, leads to a retraction of podocyte foot processes and proteinuria. This study investigates the effects of protamine sulfate or anionic, neutral, or cationic dextrans on the cytosolic calcium activity ([Ca2+]i) in podocytes. METHODS: [Ca2+]i was measured in single cultured differentiated mouse podocytes with the fluorescence dye fura-2/AM. RESULTS: Protamine sulfate caused a concentration-dependent and partially reversible increase of [Ca2+]i (EC50 approximately 1.5 micromol/liter). Pretreatment of the cells with heparin (100 U/liter) inhibited the protamine sulfate-mediated increase of [Ca2+]i. Like protamine sulfate, diethylaminoethyl dextran (DEAE-dextran) concentration dependently increased [Ca2+]i in podocytes (EC50 approximately 20 nmol/liter), whereas dextran sulfate or uncharged dextran (both 10 micromol/liter) did not influence [Ca2+]i. A reduction of the extracellular Ca2+ concentration (from 1 mmol/liter to 1 micomol/liter) partially inhibited the protamine sulfate and the DEAE-dextran-induced [Ca2+]i response. Flufenamate (100 micromol/liter) or Gd3+ (10 micromol/liter), which are known to inhibit nonselective ion channels, did not influence the [Ca2+]i increase induced by protamine sulfate. In the presence of thapsigargin (50 nmol/liter), an inhibitor of the endoplasmic reticulum Ca2+-ATPase, both protamine sulfate and DEAE-dextran increased [Ca2+]i. CONCLUSIONS: The data indicate that polycations increase podocyte [Ca2+]i. The increase of [Ca2+]i may be an early event in the pathogenesis of protamine sulfate-mediated retraction of podocyte foot processes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2005

Lipid rafts, the sarcoplasmic reticulum and uterine calcium signalling: an integrated approach.

The pathways involved in Ca2+ signalling in the uterus remain incompletely understood, impairing our ability to prevent preterm and difficult labours. In this review we focus on two elements in the pathway of Ca2+ signalling that have recently emerged as playing important roles: membrane lipid rafts and the sarcoplasmic reticulum. We examine the evidence for lipid rafts in the uterus and discuss their functional role. We suggest that the increases in cytosolic [Ca2+] and contractility that occur with raft disruption are due, at least in part, to effects on large conductance Ca2+-activated K+ (BK) channels that are localized to rafts. The role of the SR in contributing to subsarcolemmal cytosolic microdomains in uterus is evaluated, along with its interactions with ion channels on the plasma membrane. Thus, signalling microdomains play an important, but incompletely understood, role in the uterus, and integrating them into other Ca2+ signalling pathways is a challenge for further research. We suggest that the role of the SR changes in pregnancy, from promoting quiescence via BK channels or SR Ca2+ uptake, to promoting Ca2+ entry and contractility at term, and relate data on lipid rafts to clinical outcome in obese pregnant women.

Animals↗
PubMed2003

Analysis of subcellular calcium signals in T-lymphocytes.

Subcellular Ca(2+) signals were analysed in Jurkat and peripheral human T-lymphocytes by confocal Ca(2+) imaging employing an off-line deconvolution method. Stimulation of the TCR/CD3 complex in T-lymphocytes resulted in a series of subcellular pacemaker Ca(2+) signals preceding the first global Ca(2+) signal. The pacemaker signals occurred in a cytosolic "trigger" zone, which is localised close to the plasma membrane. The pacemaker signals were almost independent of extracellular Ca(2+) as shown by measurements in the absence of extracellular Ca(2+), or in the presence of the Ca(2+) channel blocker SK-F 96365. Analysis of the confocal Ca(2+) images revealed characteristic amplitudes of 82 +/- 30 to 109 +/- 21 nM, signal diameters between 2.5 +/- 0.9 and 3.5 +/- 1.5 microm and frequencies between 0.235 and 0.677 s(-1). Taken together, our data constitute the first analysis of subcellular Ca(2+) signals in T cells and indicate that the pacemaker Ca(2+) release events, which are necessary for the development of the global Ca(2+) signal, are composed of Ca(2+) release both from inositol 1,4,5-trisphosphate- and ryanodine receptors.

Calcium↗
PubMed2002

Receptor-activated calcium signals in tangentially migrating cortical cells.

Recent studies have shown that the two main types of cortical neurons, pyramidal and nonpyramidal, have different origins and use different migratory routes--radial and tangential respectively. The role of neurotransmitters in radial migration is well known; however, there are no data about their effect on intracellular calcium--[Ca(2+)](i)--in tangentially migrating cells. We have performed ratiometric and confocal calcium imaging of 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine labelled tangentially migrating neurons in the intermediate zone cells of fetal rat coronal slices. Superfusion with N-methyl-D-aspartic acid (NMDA) leads to an increase in [Ca(2+)](i), which is blocked by the antagonist APV or the presence of Mg(2+) in the medium. Kainate produced an increase in [Ca(2+)](i) that could be blocked by the non-NMDA antagonist CNQX. Muscimol, an agonist of GABAa-receptors, produced a transitory increase in [Ca(2+)](i) that was blocked by the specific antagonist bicuculline or the presence of tetrodotoxin in the medium. We conclude that tangentially migrating cells display consistent [Ca(2+)](i) changes in response to agonists of NMDA, non-NMDA and GABAa receptors, suggesting that these cells are quite mature and homogeneous. The endogenous activation of these receptors may have either a direct effect on tangential migration or modulate the response of migrating cells to external cues.

2-Amino-5-phosphonovalerate↗
PubMed2003

Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling.

Vesl/Homer proteins physically link proteins that mediate cellular signaling [Curr. Opin. Neurobiol. 10 (2000) 370; Trends Neurosci. 23 (2000) 80; J. Cell Sci. 113 (2000) 1851] and thereby influence cellular function [Nat. Neurosci. 4 (2001) 499; Nature 411 (2001) 962]. A previous study reported that Vesl-1L/Homer-1c (V-1L) controls the gain of the intracellular calcium activated calcium channel ryanodine receptor type 1 (RyR1) channel [J. Biol Chem. 277 (2002) 44722]. Here, we show that the function of RyR1 is differentially regulated by two isoforms of Vesl-1/Homer-1, V-1L and Vesl-1S/Homer-1a (V-1S). V-1L increases the activity of RyR1 while important regulatory functions and pharmacological characteristics are preserved. V-1S alone had no effect on RyR1, even though, like V-1L, it is directly bound to the channel. However, V-1S dose-dependently decreased the effects of V-1L on RyR1, providing a novel mechanism for the regulation of intracellular calcium channel activity and calcium homeostasis by changing expression levels of Vesl/Homer proteins.

Animals↗
PubMed2004

Morphological and functional changes of dissociated single pancreatic acinar cells: testing the suitability of the single cell as a model for exocytosis and calcium signaling.

Isolated single pancreatic acinar cells have long been used as a model for studying many kinds of signaling processes due to their structural and functional polarities, but without significant validation. In this study, we examined the morphological and functional changes of dissociated single pancreatic acinar cells. Acutely isolated single cells showed a collapsed membrane potential and a much reduced secretion of zymogen granules in response to acetylcholine (ACh) stimulation, whereas clustered cells showed a much more negative membrane potential and potent exocytotic secretion. The isolated single cells became vertically flattened due to the loss of supporting adhesions with nearby cells, and the granule-attached luminal membrane was severely reduced versus that of clustered cells. However, polarized Ca(2+) signals and mitochondrial localizations were relatively well preserved in the isolated single cells, in that Ca(2+) release by ACh commenced at the indented luminal membrane. In clusters, the Ca(2+) release site was closest to the lumen where more than three cells met or at the tips of conical regions of the luminal membrane. These findings suggest that the dissociated single pancreatic acinar cells preserve an intact Ca(2+) signaling machinery but alter in shape and have impaired exocytotic functions and resting membrane potentials.

Acetylcholine↗
PubMed2002

Src modulates serotonin-induced calcium signaling by regulating phosphatidylinositol 4,5-bisphosphate.

We tested the hypothesis that, in airway smooth muscle cells, stimulation of G-protein-coupled receptors by contractile agonists activates Src kinase and that this kinase modulates cell contractility and Ca(2+) signaling by affecting the levels of the phospholipase C substrate phosphatidylinositol 4,5-bisphosphate (PIP(2)). Stimulation of cultured rat tracheal smooth muscle cells with serotonin (5-HT) induced an increase in Src activity, Ca(2+) mobilization, and contraction (decrease in cell area). 5-HT-evoked cell contraction was reduced by a specific inhibitor of Src family kinases, 4-amino-5(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1). Peak Ca(2+) responses to 5-HT were attenuated by PP1 and an anti-Src-blocking antibody and augmented by expression of constitutively activated Y529F Src. Sustained phases of Ca(2+) responses to 5-HT and Ca(2+) influx resulting from emptying of Ca(2+) stores in the endoplasmic reticulum by thapsigargin were also decreased after PP1 treatment. PP1 significantly reduced the turnover of inositol phosphates produced on 5-HT stimulation and the amount of PIP(2) in the Triton X-100-insoluble lipid fraction. Overall, these data demonstrate that, in rat tracheal smooth muscle cells, Src kinase modulates 5-HT-evoked cell contractility and Ca(2+) signaling by regulating PIP(2) levels and Ca(2+) influx.

Animals↗
PubMed2002

Changes in calcium signaling during postembryonic dendritic growth in Manduca sexta.

Activity-dependent Ca(2+) influx plays crucial roles in adult and developing nervous systems through its influence on signal processing, synaptic plasticity, and neuronal differentiation. The responses to internal Ca(2+) elevations vary depending on the spatial distribution of Ca(2+) accumulation in different cell compartments. In this study, the mechanisms and the distribution of Ca(2+) accumulation are addressed by in situ Ca(2+) imaging of an identified insect motoneuron, MN5, at critical stages of postembryonic life. During metamorphosis of Manduca sexta, MN5 undergoes extensive dendritic regression followed by regrowth. The time course, amplitude, and distribution of Ca(2+) accumulation within MN5 change during development. During the initial stage of rapid dendritic growth and branching, dendritic growth cones are present, and voltage-dependent Ca(2+) currents are small. At this stage, activity-induced elevations of internal Ca(2+) are largest in the distal dendrites, suggesting that the density of voltage-gated Ca(2+) channels is highest in these regions. Later phases of dendritic growth are accompanied by the transient occurrence of prominent Ca(2+) spikes. Single Ca(2+) spikes cause robust Ca(2+) influx of similar amplitudes and time courses in all central compartments of MN5. The resting Ca(2+) levels also increase during development. Ca(2+)-induced Ca(2+) release from intracellular stores did not contribute to the elevations measured at either stage, although Ca(2+) stores are present in the dendrites. These developmental changes of the internal Ca(2+) signaling are consistent with a regulatory role for activity-dependent Ca(2+) influx in postembryonic dendritic growth.

Action Potentials↗
PubMed2000

Calcium signalling mediated by the 9 acetylcholine receptor in a cochlear cell line from the immortomouse.

1. We have investigated the characteristics of the alpha9 acetylcholine receptor (alpha9AChR) expressed in hair cell precursors in an immortalized cell line UB/OC-2 developed from the organ of Corti of the transgenic H-2Kb-tsA58 mouse (the Immortomouse) using both calcium imaging and whole-cell recording. 2. Ratiometric measurements of fura-2 fluorescence revealed an increase of intracellular calcium concentration in cells when challenged with 10 microM ACh. The calcium increase was seen in 66 % of the cells grown at 39 degrees C in differentiated conditions. A sm aller fraction (34%) of cells grown at 33 degrees C in proliferative con ditions responded. 3. Caffeine (10mM) elevated cell calcium. In the ab sence of caffeine, the majority of imaged cells responded only once to A Ch presentations. Pretreatment with caffeine ingibited all calcium respo nses to ACh. 4. In whole-cell tight-seal recordings 10 microM ACh activa ted inward current was dependent on the extracellular calcium concentrat ion with an estimated PCa/PNa of 80 for the alpha9 receptor at physiological calcium levels. 5 . The data indicate that ACh activates a calcium-permeable channel alpha 9AChR in UB/OC-2 cells and that the channel has a significantly higher c alcium permeability than other AChRs. The results indicate that the alp ha9AChR may be able to elevate intracellular calcium levels in hair cell s both directly and via store release.

Acetylcholine↗
PubMed1999

Calcium signalling in cardiac muscle: refractoriness revealed by coherent activation.

Contraction of cardiac myocytes is governed by calcium-ion (Ca2+ )-induced Ca2+ release (CICR) from the sarcoplasmic reticulum through Ca2+-release channels. Ca2+ release occurs by concerted activation of numerous elementary Ca2+ events, 'Ca2+ sparks', that are triggered and locally controlled by Ca2+ influx into the cell through plasmalemmal L-type Ca2+ channels. Because of the positive feedback inherent in CICR, an as-yet-unidentified control mechanism is required to restrain the amplification of Ca2+ signalling and to terminate Ca2+ release from the sarcoplasmic reticulum. Here we use ultraviolet-laser-flash and two-photon photolysis of caged Ca2+ to study spatiotemporal features of the termination and refractoriness of Ca2+ release. Coherent and simultaneous activation of all Ca2+-release sites within a cardiac myocyte unmasked a prominent refractoriness, recovering monotonically within about 1 second. In contrast, selective activation of a few Ca 2+-release sites was not followed by a refractoriness of Ca 2+ release from the sarcoplasmic reticulum. This discrepancy is consistent with the idea that a functional depletion of Ca2+ from the cellular sarcoplasmic-reticulum network may underlie the refractoriness of CICR observed after a whole-cell Ca2+ transient. These results also imply the requirement for further mechanisms to terminate spatially limited subcellular Ca2+-release events such as Ca2+ sparks.

Animals↗
PubMed2006

Calcium signals mediated by STIM and Orai proteins--a new paradigm in inter-organelle communication.

In all cells Ca2+ signals are key to controlling a spectrum of cellular responses. Ca2+ signals activated by phospholipase C-coupled receptors have two components-rapid Ca2+ release from ER stores followed by slower Ca2+ entry from outside the cell. The coupling process between ER and PM to mediate this "store-operated" Ca2+ entry process has remained a molecular and mechanistic mystery. Through a combination of high throughput screening and molecular physiological approaches, the machinery and mechanism of this process have been elucidated. Two proteins are key to the coupling process. STIM1, a single spanning membrane protein with an unpaired Ca2+ binding EF-hand functions as the sensor of ER luminal Ca2+ and through redistribution in the ER transduces information directly to the PM. Orai1, a tetra-spanning PM protein, functions as the highly Ca2+ selective channel in the PM that is gated through interactions with the store-activated ER Ca2+ sensor. This molecular pas-de-deux between ER and PM components represents not only a crucial signaling pathway, but also a new paradigm in inter-organelle communication.

Amino Acid Sequence↗
PubMed2003

Activation of calcium signaling by hepatitis B virus-X protein in liver cells.

Hepatitis B virus x gene product (HBx) is known to be a transactivator of transcriptional elements that regulate the expression of a variety of genes associated with the growth, differentiation, survival and the apoptosis of cells. However, the exact mechanism of the activation and inhibition of cellular events by HBx remains uncertain. The present study was designed to measure the effect of HBx, on the signal transduction pathways associated with intracellular Ca(2+) mobilization following HBx transfection in the stable Chang liver cells (CHL-X). Enhanced cell proliferation by HBx in CHL-X was confirmed by MTT assay and by the immunodetection of PCNA. The transactivation of AP-1 by HBx induced in CHL-X was inhibited by cyclosporin A (CsA), a mitochondrial Ca(2+) channel blocker and by BAPTA-AM, a cytosolic Ca(2+) blocker. Activation of the SAPK/JNK signaling pathway by HBx was evidenced by the increased phosphorylations of c-Jun (Ser63) and of JNK (Thr183/Tyr185). Increased phospho-Erk/Erk and phospho-Raf1/Raf in HBx-induced CHL-X indicated that HBx might stimulate the MAPK pathway. PI3K activity and cytosolic free Ca(2+) levels were elevated in HBx-induced CHL-X. These results imply that HBx transactivates both JNK and MAPK signal transduction pathways in association with the mobilization of cytosolic Ca(2+).

Calcium↗
PubMed2003

Intracellular calcium signaling through the cADPR pathway is agonist specific in porcine airway smooth muscle.

Cyclic ADP-ribose (cADPR) induces intracellular Ca2+ ([Ca2+]i) release in airway smooth muscle, and the cADPR antagonist, 8-amino-cADPR, abolishes [Ca2+]i oscillations elicited by acetylcholine (ACh), suggesting that cADPR is involved during muscarinic receptor activation. Whether the cADPR signaling pathway is common to agonists acting through different G protein-coupled receptors is not known. Using digital video imaging of Fura2-AM loaded porcine airway smooth muscle cells, we examined the effects of the membrane-permeant cADPR antagonist, 8-bromo-cADPR (8Br-cADPR), on the [Ca2+]i responses to ACh, histamine and endothelin-1 (ET-1). In cells preincubated with 100 microM 8Br-cADPR, the [Ca2+]i responses to ACh and ET-1 were significantly attenuated, whereas responses to histamine were not, suggesting agonist specificity of cADPR signaling. The effects of 8Br-cADPR were concentration dependent. We further examined whether muscarinic receptor subtypes specifically couple to this pathway, because in porcine airway smooth muscle cells, ACh activates both M2 and M3 muscarinic receptors coupled to Gai and Gaq, respectively. Methoctramine, an M2-selective antagonist, attenuated the [Ca2+]i responses to Ach, and there was no further attenuation by 8Br-cADPR. In airway smooth muscle, the CD38/cADPR signaling pathway is involved in [Ca2+]i responses to contractile agonists in an agonist-specific manner.

Animals↗