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Results for “Calcium Signaling”

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At least 1,009 records · Page 56Linked to original sources
PubMed2002

A role for phosphorylation of inositol 1,4,5-trisphosphate receptors in defining calcium signals induced by Peptide agonists in pancreatic acinar cells.

Stimulation of pancreatic acinar cells with acetylcholine (ACh) and cholecystokinin (CCK) results in an elevation of cytosolic calcium ([Ca(2+)](c)) through activation of inositol 1,4,5-trisphosphate receptors (InsP(3)R). The global temporal pattern of the [Ca(2+)](c) changes produced by ACh or CCK stimulation differs significantly. The hypothesis was tested that CCK stimulation results in a protein kinase A (PKA)-mediated phosphorylation of InsP(3)R and this event contributes to the generation of agonist-specific [Ca(2+)](c) signals. Physiological concentrations of CCK evoked phosphorylation of the type III InsP(3)R, which was blocked by pharmacological inhibition of PKA. Imaging of fura-2-loaded acinar cells revealed that the rate of [Ca(2+)](c) rise during CCK-evoked oscillations slows with each subsequent oscillation, consistent with a developing modulation of release, whereas the kinetics of ACh-evoked oscillations remain constant. Stimulation of cells with ACh following activation of PKA resulted in a slowing of the ACh-evoked [Ca(2+)](c) rise, which now resembled a time-matched CCK response. PKA activation also resulted in a slowing of [Ca(2+)](c) increases elicited by photolysis of caged InsP(3). Targeted, PKA-mediated phosphorylation of type III InsP(3)R is involved in a physiological CCK response, as disruption of the targeting of PKA with the peptide HT31 resulted in marked changes in the CCK-evoked [Ca(2+)](c) signal but had no effect on ACh-evoked responses. Stimulation of cells with bombesin, which evokes [Ca(2+)](c) oscillations indistinguishable from those produced by CCK, also results in PKA-mediated phosphorylation of type III InsP(3)R. Thus, we conclude that PKA-mediated phosphorylation of type III InsP(3)R is a general mechanism by which the patterns of [Ca(2+)](c) oscillations are shaped in pancreatic acinar cells.

Acetylcholine↗
PubMed2002

Ca2+ marks: miniature calcium signals in single mitochondria driven by ryanodine receptors.

Propagation of cytosolic [Ca(2+)] ([Ca(2+)](c)) signals to the mitochondria is believed to be supported by a local communication between Ca(2+) release channels and adjacent mitochondrial Ca(2+) uptake sites, but the signaling machinery has not been explored at the level of elementary Ca(2+) release events. Here, we demonstrate that [Ca(2+)](c) sparks mediated by ryanodine receptors are competent to elicit miniature mitochondrial matrix [Ca(2+)] signals that we call "Ca(2+) marks." Ca(2+) marks are restricted to single mitochondria and typically last less than 500 ms. The decay of Ca(2+) marks relies on extrusion of Ca(2+) from the mitochondria through the Ca(2+) exchanger, whereas [Ca(2+)](c) sparks decline primarily by diffusion. Mitochondria also appear to have a direct effect on the properties of [Ca(2+)](c) sparks, because inhibition of mitochondrial Ca(2+) uptake results in an increase in the frequency and duration of [Ca(2+)](c) sparks. Thus, a short-lasting opening of a cluster of Ca(2+) release channels can yield activation of mitochondrial Ca(2+) uptake, and the competency of mitochondrial Ca(2+) handling may be an important determinant of cardiac excitability through local feedback control of elementary [Ca(2+)](c) signals.

Animals↗
PubMed1995

Calcium signals in olfactory neurons.

Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

Aniline Compounds↗
PubMed2005

SET-induced calcium signaling and MAPK/ERK pathway activation mediate dendritic cell-like differentiation of U937 cells.

Human SET, a target of chromosomal translocation in human leukemia encodes a highly conserved, ubiquitously expressed, nuclear phosphoprotein. SET mediates many functions including chromatin remodeling, transcription, apoptosis and cell cycle control. We report that overexpression of SET directs differentiation of the human promonocytic cell line U937 along the dendritic cell (DC) pathway, as cells display typical morphologic changes associated with DC fate and express the DC surface markers CD11b and CD86. Differentiation occurs via a calcium-dependent mechanism involving the CaMKII and MAPK/ERK pathways. Similar responses are elicited by interferon-gamma (IFN-gamma) treatment with the distinction that IFN-gamma signaling activates the DNA-binding activity of STAT1 whereas SET overexpression does not. In addition, unlike IFN-gamma signaling, SET generated stress-induced p38/MAPK activity. Interestingly, IFN-gamma treatment transiently upregulated endogenous SET in a dose-dependent manner. These results suggest that SET is part of both IFN-gamma-mediated and stress-mediated cellular responses and that SET induces cell differentiation via calcium and MAPK/ERK pathways.

Calcium Signaling↗
PubMed1993

Potential role of 12 hydroxyeicosatetraenoic acid in angiotensin II-induced calcium signal in rat glomerulosa cells.

Recent evidence suggests that 12 hydroxyeicosatetraenoic acid (12HETE), a product of the 12 lipoxygenase (LO) pathway of arachidonic acid metabolism, may have a role in mediating angiotensin II (AII)-induced aldosterone secretion. The present study examined the possible role of the 12 LO product 12HETE in AII-induced calcium ([Ca++]i) signals in rat glomerulosa cells. The addition of 12HETE to glomerulosa cells induced a dose-dependent (10(-6)-10(-8) M) rise in [Ca++]i levels that was sustained over 15 min. The effects of 12HETE on [Ca++]i were attenuated but not blocked by nifedipine (5 x 10(-6) M) and were preserved in a calcium-free medium, suggesting mobilization of intracellular calcium stores. Furthermore, the 12HETE-mediated rise in [Ca++]i was almost entirely abolished by dantrolene. In parallel, 12HETE reversed the inhibitory effect of nifedipine on AII-induced aldosterone secretion [AII (10(-9) M) - 36 +/- 7, AII + nifedipine (5 x 10(-6) M) - 13 +/- 2, AII + nifedipine + 12HETE (5 x 10(-8) M) - 27 +/- 4 ng/10(6) cells]. Dantrolene also inhibited AII-dependent aldosterone secretion (AII 10(-9) M - 75.8 +/- 5.6, AII + dantrolene 10(-6) M 45.5 +/- 8.8 ng/10(-6) cells), but this inhibition could not be reversed by 12HETE 10(-8) M (45.4 +/- 10.6 ng/10(6) cells). The LO blockers baicalein and BW755C inhibited the effect of AII on aldosterone production and on [Ca++]i in a parallel fashion. During LO blockade, the addition of 12HETE (10(-7) M) restored the AII-induced rise in [Ca++]i. Collectively, these observations suggest that activation of the LO pathway in the rat adrenal glomerulosa contributes to change in cytosolic calcium, which may be important for the steroidogenic effect of AII.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2005

Proliferation, cell cycle exit, and onset of terminal differentiation in cultured keratinocytes: pre-programmed pathways in control of C-Myc and Notch1 prevail over extracellular calcium signals.

So far it was reported that a switch from low to high extracellular calcium induces growth arrest and terminal differentiation in cultured human and mouse keratinocytes. We had observed that both canine and mouse keratinocytes proliferate in high (1.8 mM, respectively, 1.2 mM) or low (0.09 and 0.06 mM) calcium-containing medium. In-depth analysis of this phenomenon revealed, as reported here, that the switch between proliferation and terminal differentiation occurred irrespective of calcium conditions when the canine and murine keratinocytes reach confluency. The "confluency switch" coincided with transcriptional upregulation of cell cycle inhibitors p21(WAF1) and p27(KIP1) as well as proteins marking onset of terminal differentiation. It was further accompanied by downregulation and nuclear clearance of c-Myc, and conversely activation of Notch1, which are shown to be critical determinants of this process. Together, this study demonstrates that even in the absence of and similar to their in vivo environment, cultured canine and mouse keratinocytes follow a pre-defined differentiation program. This program is in control of c-Myc and Notch1 and does not require complementary signals for onset of terminal differentiation except those given by cell-cell contact. Once triggered, completion of the terminal differentiation process depends on elevated extracellular calcium to stabilize intercellular junctions and components of the cornified envelope.

Animals↗
PubMed2005

Depolarization evokes different patterns of calcium signals and exocytosis in bovine and mouse chromaffin cells: the role of mitochondria.

This study was planned on the assumptions that different high-voltage activated calcium channels and/or the ability of mitochondria to take up Ca(2+) could be responsible for different cytosolic Ca(2+) concentrations ([Ca(2+)](c)) and catecholamine release responses in adrenal chromaffin cells of bovine and mouse species. Short K(+) pulses (2-5 s, 70 mM K(+)) increased [Ca(2+)](c) to a peak of about 1 microM; however, in bovine cells the decline was slower than in mouse cells. Secretory responses were faster in mouse but were otherwise quantitatively similar. Upon longer K(+) applications (1 min), elevations of [Ca(2+)](c) and secretion were prolonged in bovine cells; in contrast [Ca(2+)](c) in mouse cells declined three-fold faster and failed to sustain a continued secretion. Confocal [Ca(2+)](c) imaging following a 50-ms depolarizing pulse showed a similar Ca(2+) entry, but a rate of [Ca(2+)](c) increase and a maximum peak significantly higher in bovine cells; the rate of dissipation of the Ca(2+) wave was faster in the mouse. The mitochondrial protonophore CCCP (2 microm) halved the K(+)-evoked [Ca(2+)](c) and secretory signals in mouse cells, but had little affect on bovine responses. We conclude that the relative densities of L (15% in bovine and 50% in mouse) and P/Q Ca(2+) channels (50% in bovine and 15% in mouse) do not contribute to the observed differences; rather, the different intracellular distribution of Ca(2+), which is strongly influenced by mitochondria, is responsible for a more sustained secretory response in bovine, and for a faster and more transient secretory response in mouse chromaffin cells. It seems that mitochondria near the plasmalemma sequester Ca(2+) more rapidly and efficiently in the mouse than in the bovine chromaffin cell.

Aniline Compounds↗
PubMed1995

Adrenergic calcium signaling in astrocyte networks within the hippocampal slice.

Norepinephrine (NE) and glutamate (Glu) initiate intracellular calcium ([Ca2+]i) transients, oscillations, and intracellular [Ca2+]i waves in cultured astrocytes. To further elucidate the significance of NE- and Glu-evoked astrocytic [Ca2+]i signaling to neuron-astrocyte communication in the mature CNS, [Ca2+]i of astrocyte networks within hippocampal slices (P21-42) was measured during bath application of NE and Glu receptor agonists. Astrocytes in stratum radiatum were identified by highly negative membrane potentials (75 +/- 3 mV), absence of action potentials, and dye coupling following intracellular injection of the [Ca2+]-sensitive dye calcium orange. NE (2-100 microM) evoked [Ca2+]i increases (7 of 8 slices, 24 of 24 cells in responding slices) characterized by an initial rise, 20-50 sec to peak, followed by a slower return to baseline (over approximately 8 min). The alpha 1-agonist phenylephrine (PE) (10-100 microM) evoked complex [Ca2+]i signals (22 of 26 slices, 90 of 90 cells in responding slices) composed of both a prolonged component (5.1 +/- 1.8 min), synchronized in neighboring cells, and multiple, mainly asynchronous [Ca2+]i spikes (25.0 +/- 11.6 sec). PE responses were completely blocked by the alpha 1-antagonist prazosin (200 nM, n = 4 slices), but not by the alpha 2-antagonist yohimbine (n = 3 slices). The alpha 2-agonist clonidine (10-100 microM) did not increase [Ca2+]i (n = 4 slices). alpha 1-mediated [Ca2+]i transients were observed after removal of extracellular [Ca2+]o (n = 8 of 9 slices), indicating PE-induced Ca2+ release from intracellular stores. Adrenergic responses were mediated by alpha 1-receptors localized to astrocytes because PE and NE increased [Ca2+]i of acutely isolated hippocampal astrocytes. Glu (0.75-2.0 mM) did not increase astrocytic [Ca2+]i in slices (0 of 7), even in the presence of the Glu uptake inhibitor L-trans-pyrrollidine-2,4-dicarboxylic acid (PDC) (0 of 5 slices), or in acutely isolated astrocytes (0 of 7 cells). The metabotropic agonist t-ACPD (30 or 50 microM) did not increase astrocytic [Ca2+]i in hippocampal slices (0 of 5), while kainate (200 microM or 1 mM) induced brief (1-2 min) [Ca2+]i increases only rarely (2 of 8 applications in 6 slices). These results support a primary role of NE release and alpha 1-adrenoceptor stimulation in neuron-astrocyte communication in the mature CNS.

Animals↗
PubMed1999

Coactivation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells.

In primary culture of mouse cerebellar granule cells, the brain-derived neurotrophic factor (BDNF) gene is activated in an activity-dependent manner, accompanying Ca2+ influx into neurons through voltage-dependent calcium channels (VDCCs). In this study, we investigated the inducibility of secretogranin-II (Sg-II) gene in terms of Ca2+ signals evoked via VDCCs, by a comparison with BDNF and c-fos genes. Deprivation and subsequent induction of membrane depolarization by lowering and reelevating the extracellular concentration of potassium chloride (KCl), respectively, led to an decrease and then an increase in the Sg-II, BDNF and c-fos mRNA expression. The increase in Sg-II mRNA expression was detected as early as but was slower than that of BDNF one. The increase in Sg-II mRNA expression was induced depending upon the extracellular Ca2+ and inhibited by nicardipine, indicating a requirement of Ca2+ influx through VDCCs for the Sg-II as well as BDNF gene induction. Inhibition of de novo protein synthesis by cycloheximide did not affect the Sg-II induction. The response of Sg-II gene to the changes in extracellular KCl concentration was the same as that of BDNF but different from that of c-fos gene. Thus, Sg-II gene is coactivated with BDNF gene in response to the intracellular Ca2+ signals evoked via Ca2+ influx through VDCCs.

Animals↗
PubMed1991

Attachment of A172 human glioblastoma cells affects calcium signalling: a comparison of image cytometry, flow cytometry, and spectrofluorometry.

The intracellular free calcium concentration ([Ca2+]i) of indo-1 loaded A172 human glioblastoma cells stimulated by platelet-derived growth factor (PDGF) was studied in cell suspensions by flow cytometry and spectrofluorometry and in confluent monolayers by laser image cytometry and spectrofluorometry. With all three techniques, the percentage of responsive cells, peak [Ca2+]i, and the duration of response were directly related, and the delay time was inversely related to PDGF dose. The maximum response occurred at a PDGF concentration of about 20 ng/ml. Basal and peak [Ca2+]i did not differ significantly from method to method even though different calibration procedures were used. Cells in suspension monitored by both spectrofluorometry and flow cytometry displayed significantly shorter calcium responses than attached cells. This did not appear to be a direct effect of trypsinization. Spectral analysis of indo-1 in cytoplasm, 40% glycerol, and aqueous solutions showed significant differences in the isosbestic point and quantum efficiency. Calibration of [Ca2+]i with spectrofluorometry is more accurate using the ratio of fluorescence intensities than the fluorescence intensities measured at either 405 or 485 nm.

Calcium↗
PubMed1992

Integration of cytoplasmic calcium and membrane potential oscillations maintains calcium signaling in pituitary gonadotrophs.

Pituitary gonadotrophs exhibit spontaneous low-amplitude fluctuations in cytoplasmic calcium concentration ([Ca2+]i) due to intermittent firing of nifedipine-sensitive action potentials. The hypothalamic neuropeptide, gonadotropin-releasing hormone, terminates such spontaneous [Ca2+]i transients and plasma-membrane electrical activity and initiates high-amplitude [Ca2+]i oscillations and concomitant oscillations in membrane potential (Vm). The onset of agonist-induced [Ca2+]i oscillations is not dependent on Vm or extracellular Ca2+ but is associated with plasma-membrane hyperpolarization interrupted by regular waves of depolarization with firing of action potentials at the peak of each wave. The Vm and Ca2+ oscillations are interdependent during continued gonadotropin-releasing hormone action (greater than 3-5 min), when sustained Ca2+ entry is necessary for the maintenance of [Ca2+]i spiking. The initial and sustained agonist-induced Ca2+ transients and Vm oscillations are abolished by blockade of endoplasmic reticulum Ca(2+)-ATPase, consistent with the role of Ca2+ re-uptake by internal stores in the oscillatory response during both phases. Such a pattern of synchronization of electrical activity and Ca2+ spiking in cells regulated by Ca(2+)-mobilizing receptors shows that the operation of the cytoplasmic oscillator can be integrated with a plasma-membrane oscillator to provide a long-lasting signal during sustained agonist stimulation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

Lysophosphatidic acid-induced calcium signals in cultured rat oligodendrocytes.

Oligodendrocytes are the myelin forming glial cells of the CNS and are known to express receptors linked to ion channels and intracellular second messenger cascades. In this paper, we describe the intracellular calcium responses of cells from the oligodendrocyte lineage to application of lysophosphatidic acid (LPA), a naturally occurring, growth factor-like phospholipid. Oligodendrocyte precursors did not respond to application of LPA (1 microM). In mature oligodendrocytes, however, LPA (1 microM) induced an increase in the intracellular calcium concentration ([Ca2+]i). In the majority of cells this increase was followed by a persistent plateau phase. The LPA-induced [Ca2+]i signal vanished in Ca2+-free medium, implying that it arose due to a Ca2+ influx across the plasma membrane. Preincubation of the cells with Pertussis-toxin prevented the generation of LPA-induced [Ca2+]i signals. We conclude that cultured rat oligodendrocytes express functional LPA receptors, which mediate a transmembrane Ca2+ influx via a Pertussis-toxin-sensitive G-protein.

Animals↗