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At least 685 records · Page 38Linked to original sources
PubMed2002

Release from intracellular stores is responsible for calcium signaling with von Willebrand factor in human platelets.

Interaction of von Willebrand factor (VWF) with the platelet promotes hemostasis upon vascular injury. Such interaction raises intracellular free calcium concentration ([Ca2+]i) and induces platelet activation. The platelet [Ca2+]i increase is generally attributed to influx across the plasma membrane. The present study defined the contribution of intracellular calcium stores. Platelet [Ca2+]i was monitored with Fura-PE3. Ristocetin-mediated binding of VWF transiently elevated [Ca2+]i after a lag phase. Studies with 63 healthy donors consistently revealed a VWF-induced platelet [Ca2+]i signal in the absence of extracellular calcium; there was only modest enhancement with extracellular calcium. Blockade of plasma membrane calcium channels did not diminish the signal, whereas depletion or blockade of the intracellular calcium stores abolished it. These findings imply that release from intracellular stores is responsible for the VWF-induced platelet [Ca2+]i increase. Influx across the plasma membrane plays no more than a minor role, probably representing "capacitative entry" to refill the intracellular stores.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2005

CRF-induced calcium signaling in guinea pig small intestine myenteric neurons involves CRF-1 receptors and activation of voltage-sensitive calcium channels.

Corticotropin-releasing factor (CRF) is a 41-amino acid peptide with distinct effects on gastrointestinal motility involving both CRF-1 and CRF-2 receptor-mediated mechanisms that are generally claimed to be centrally mediated. Evidence for a direct peripheral effect is rather limited. Electrophysiological studies showed a cAMP-dependent prolonged depolarization of guinea pig myenteric neurons on application of CRF. The current study aimed to test the direct effect of CRF on myenteric neurons and to identify the receptor subtype and the possible mechanisms involved. Longitudinal muscle myenteric plexus preparations and myenteric neuron cultures of guinea pig small intestine were incubated with the calcium indicator Fluo-4. Confocal Ca(2+) imaging was used to visualize activation of neurons on application of CRF. All in situ experiments were performed in the presence of nicardipine 10(-6) M to reduce tissue movement. Images were analyzed using Scion image and a specifically developed macro to correct for residual minimal movements. A 75 mM K(+)-Krebs solution identified 1,076 neurons in 46 myenteric ganglia (16 animals). Administration of CRF 10(-6) M and CRF 10(-7) M during 30 s induced a Ca(2+) response in 22.4% of the myenteric neurons (n = 303). Responses were completely abolished in the presence of the nonselective CRF antagonist astressin (n = 55). The selective CRF-1 receptor antagonist CP 154,526 (n = 187) reduced the response significantly to 2.1%. Stresscopin, a CRF-2 receptor agonist, could not activate neurons at 10(-7) M, and its effect at 10(-6) M (15.3%, n = 59) was completely blocked by CP 154,526. TTX 10(-6) M (n = 70) could not block the CRF-induced Ca(2+) transients but reduced the amplitude of the signals significantly. Removal of extracellular Ca(2+) blocked all responses to CRF (n = 47). L-type channels did not contribute to the CRF-induced Ca(2+) transients. Blocking N- or P/Q-type Ca(2+) channels did not reduce the responses significantly. Combined L- and R-type Ca(2+) channel blocking (SNX-482 10(-8) M, n = 64) abolished nearly all responses in situ. Combined L-, N-, and P/Q-type channel blocking also significantly reduced the response to 8.6%. Immunohistochemical staining for CRF-1 receptors clearly labeled individual cell bodies in the ganglia, whereas the CRF-2 receptor staining was barely above background. CRF induces Ca(2+) transients in myenteric neurons via a CRF-1 receptor-dependent mechanism. These Ca(2+) transients highly depend on somatic calcium influx through voltage-operated Ca(2+) channels, in particular R-type channels. Action potential firing through voltage-sensitive sodium channels increases the amplitude of the Ca(2+) signals. Besides centrally mediated effects, CRF is likely to modulate gastrointestinal motility on the myenteric neuronal level.

Animals↗
PubMed1998

Mechanisms of rise and decay of ADP-evoked calcium signal in MDCK cells.

We have studied the effects of ADP on intracellular calcium levels ([Ca2+]i) measured by fura-2 fluorimetry in Madin Darby canine kidney (MDCK) cells. ADP evoked [Ca2+]i rises dose-dependently by releasing Ca2+ from the inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ pool followed by capacitative Ca2+ entry. The Ca2+ signal consisted of a peak and a gradual decline which reached a plateau in the case of 0.1-1 mM ADP; a plateau was not seen in the response to 10 mM ADP. ADP acted by stimulating P2u and P2y receptors based on rank order of agonist potency: ATP = UTP > ADP > 2-methylthio-ATP > 2-methylthio-ADP > adenosine > alpha, beta-methylene ATP. Buffering by lysosomes and efflux via plasmalemmal Ca2+ pumps might play important roles in the decay of the Ca2+ signal. The Ca2+ signal was dramatically inhibited by 100 microM LaCl3.

Adenosine Diphosphate↗
PubMed2000

Tonotopic variations of calcium signalling in turtle auditory hair cells.

Turtle cochlear hair cells are electrically tuned by a voltage-dependent Ca2+ current and a Ca2+-dependent K+ current (IBK(Ca)). The effects of intracellular calcium buffering on electrical tuning were studied in hair cells at apical and basal cochlear locations tuned to 100 and 300 Hz, respectively. Increasing the intracellular BAPTA concentration changed the hair cell's resonant frequency little, but optimized tuning at more depolarized membrane potentials due to a positive shift in the half-activation voltage (V ) of the IBK(Ca). The shift in V depended similarly on BAPTA concentration in basal and apical hair cells despite a 2. 4-fold difference in the size of the Ca2+ current at the two positions. The Ca2+ current amplitude increased exponentially with distance along the cochlea. Comparison of V values and tuning properties using different BAPTA concentrations with values measured in perforated-patch recordings gave the endogenous calcium buffer as equivalent to 0.21 mM BAPTA in low-frequency cells, and 0.46 mM BAPTA in high-frequency cells. High conductance Ca2+-activated K+ (BKCa) channels recorded in inside-out membrane patches were 2-fold less Ca2+ sensitive in high-frequency than in low-frequency cells. Confocal Ca2+ imaging using the fluorescent indicator Calcium Green-1 revealed about twice as many hotspots of Ca2+ entry during depolarization in high-frequency compared to low-frequency hair cells. We suggest that each BKCa channel is gated by Ca2+ entry through a few nearby Ca2+ channels, and that Ca2+ and BKCa channels occupy, at constant channel density, a greater fraction of the membrane area in high-frequency cells than in low-frequency cells.

Acoustic Stimulation↗
PubMedDate not supplied

Acetylcholine and cholecystokinin induce different patterns of oscillating calcium signals in pancreatic acinar cells.

Receptor-activated cytoplasmic calcium (Ca2+) oscillations have been investigated in single pancreatic acinar cells by microfluorimetry (Fura-2 as indicator). At submaximal concentrations of the agonists acetylcholine (ACh) and cholecystokinin octapeptide (CCK-8), both give rise to oscillatory changes in the cytosolic free calcium concentration ([Ca2+]i). The patterns of oscillations are markedly and consistently different for each of these two agonists. The ACh induced oscillations are superimposed upon a median elevation in background [Ca2+]i. The CCK-8 induced oscillations are of longer duration with [Ca2+]i returning to prestimulus levels between the discrete spikes. The ACh induced oscillations are rapidly abolished upon removal of extracellular Ca2+ while the CCK-8 induced oscillations persist for many minutes in the absence of external Ca2+. The CCK-8, but not the ACh, induced oscillations are increased in duration by the protein kinase C (PKC) inhibitor staurosporine and abolished by the PKC activating phorbol ester PMA. It is clear that CCK-8 and ACh do not activate receptor transduction mechanisms in an identical manner to generate oscillating [Ca2+]i signals.

Acetylcholine↗
PubMed2006

Egg activation is the result of calcium signal summation in the mouse.

Egg activation in mammals is caused by cytosolic Ca(2+) oscillations that are essential for development. However, despite increasing knowledge about signal transduction mechanisms, the functional linkage between frequency number, amplitude and duration of the Ca(2+) signal and the kinetics of pronucleus formation has not yet been defined. While a wide range of Ca(2+) signal parameters are efficient in causing egg activation, the basic rules governing how the egg integrates these signalling events are not yet clear. Thus, in the perspective of better understanding how the egg processes Ca(2+) signalling events, the objective of this study was to determine experimentally whether the efficiency of egg activation and the subsequent early developmental stages rely on Ca(2+) signalling summation. Non-fertilized, but freshly ovulated mouse eggs, were subjected to a series of repetitive Ca(2+) influxes of various patterns modulated by a non-invasive membrane electropermeabilization method. Using a combination of two suboptimal treatments we have shown that mouse eggs can sum up the effects caused by various patterns of intracellular Ca(2+) concentrations transient during the period of egg activation. In addition, overloading the intracellular milieu by repetitive Ca(2+) influxes did not seem to inhibit the process of activation. The kinetics of pronuclear formation among a population of eggs treated in the same conditions became accelerated when the total dose of Ca(2+) signal 'experienced' by the eggs was increased. The results suggested that summation of the biological effects of all Ca(2+) signals constitutes an important mode of Ca(2+) signal integration.

Animals↗
PubMed2005

Involvement of ryanodine receptors in IP3-mediated calcium signalling in neurons. A modelling approach.

Phospholipase C (PLC)-coupled metabotropic receptors trigger the release of intracellular Ca2+ through activation of IP3 receptors (IP3Rs). Increasing evidence suggests that they can also and perhaps more efficiently mobilize Ca2+ through ryanodine receptors (RyRs). We constructed a model allowing a variable PLC stimulation level (via the parameter gamma) as well as a variable involvement of RyRs (via the parameter A). The sole presence of RyRs (A not = 0) affected the basal Ca2+ concentration [Ca2+]i. To keep Ca2+ below 160 nM, we fixed the upper limit of A to 0.2, a value that is compatible with the numerical ratio between RyRs and IP3Rs in cerebellar Purkinje neurons. Metabotropic responses were simulated by abruptly raising the value of gamma to various levels. In the absence of RyRs, the model starts to oscillate with gamma=0.4. For lower levels of PLC stimulation (gamma< or =0.3), the presence of RyR is capable of triggering an oscillatory signal. When A< or =0.18, the frequency of the Ca2+ oscillations augments from 0.1 to 1.3 Hz as a function of gamma. Conversely, as the frequency increases, the amplitude of the oscillations is reduced from 1 microM to 50 nM. With higher values of A, the oscillating pattern is definitively inhibited. It is concluded that RyRs have the potentiality to strikingly affect the temporal pattern of the Ca2+ signalling triggered by IP3-related metabotropic responses.

Animals↗
PubMed1998

Calcium signalling through nucleotide receptor P2Y2 in cultured human vascular endothelium.

Microfluorometric measurements in Fura-2-loaded single cultured human vascular endothelial cells were used to characterize the intracellular calcium [Ca2+]i responses triggered by extracellular application of adenosine 5'-triphosphate (ATP) and other nucleotides. Application of ATP or uridine 5'-triphosphate (UTP) gave rise to dose-dependent elevations of [Ca2+]i in all the cells tested. At saturating concentrations of agonist, the [Ca2+]i response was biphasic, with an early peak and a sustained plateau. Unlike peak responses, the sustained Ca2+ plateau was sensitive to removal of Ca2+ from the external medium. Mn2+ quenching revealed the presence of Ca2+ influx during the agonist-induced calcium plateau. The agonist-evoked calcium plateau was inhibited in a dose-dependent manner by the Cl-channel blocker NPPB, by the divalent cation Ni2+ and by the imidazole antimycotic econazole. Previously, these compounds have been shown to block store-operated Ca2+ entry. The two phases of the agonist-evoked [Ca2+]i response were blocked by the specific phospholipase C inhibitor U-73122 and by intracellular injection of low molecular weight heparin, suggesting the involvement of IP3-sensitive intracellular Ca2+ stores. The pharmacological profile of the response, using different nucleotides and analogues, ATP = UTP > ADP = UDP, and no responses to P2X1 and P2Y1 agonists, suggested the involvement of P2Y2 receptors. The expression of mRNA for the P2Y2 receptor was detected by RT-PCR analysis. These results indicate that P2Y2 receptors linked to intracellular Ca2+ mobilization are present in human vascular endothelial cells. The initial [Ca2+]i mobilization is followed by a phase of elevated [Ca2+]i influx.

Adenosine Triphosphate↗
PubMed1994

Modulation by sphingolipids of calcium signals evoked by epidermal growth factor.

Receptor-activated breakdown of complex sphingolipids has been proposed as a mechanism for generating sphingoid base-containing putative second messenger molecules whose actions may modulate responses to extracellular signals. In human epidermoid carcinoma A431 cells, sphingosine (1-10 microM) by itself had no effect on intracellular free calcium concentrations ([Ca2+]i), yet within seconds, markedly enhanced the epidermal growth factor (EGF)-evoked Ca2+ influx (by up to 2-fold), but failed to alter Ca2+ release from the intracellular stores. Ca2+ signals evoked by serum were not affected by sphingosine. The response to sphingosine was dose-dependent and saturable, exhibiting an EC50 of 2.3 microM. In contrast, a ceramide, N-acetylsphingosine (10 microM), sphingosine 1-phosphate (10 microM), and sphingosylphosphorylcholine (10 microM) inhibited EGF-evoked elevations in [Ca2+]i. The latter two compounds by themselves transiently increased [Ca2+]i. N-Octanoylsphingosine, N,N-dimethylsphingosine, sphingomyelin, and stearylamine were inactive. The potentiation of calcium signals by sphingosine occurred at all concentrations of EGF tested (0.15-15 nM) and did not alter the EGF receptor protein kinase activity as determined by antiphosphotyrosine immunoblotting. Antiphosphoserine immunoblotting revealed that sphingosine (10 microM for 3 min) increased the phosphoserine content of two proteins with approximate molecular masses of 40 and 70 kDa. Serine hyperphosphorylation of the 40-kDa protein was also observed in cells treated with EGF alone, whereas the intensity of the 70-kDa band was highest in cells treated with both sphingosine and EGF. The modulation of growth factor receptor-regulated signaling, including changes in [Ca2+]i, may constitute a mechanism by which elevations in cellular levels of specific sphingolipids, which occur transiently upon activation of certain receptors and chronically in sphingolipid storage diseases, exert their physiological and pathophysiological effects.

Calcium↗
PubMed1996

Mechanical stimulation initiates cell-to-cell calcium signaling in ovine lens epithelial cells.

Although abnormalities in calcium regulation have been implicated in the development of most forms of cataract, the mechanisms by which Ca2+ is regulated in the cells of the ocular lens remain poorly defined. Cell-to-cell Ca2+ signaling was investigated in primary cultures of ovine epithelial cells using the Ca(2+)-reporter dye fura-2 and fluorescence microscopy. Mechanical stimulation of a single cell with a micropipette initiated a propagated increase in cytosolic free Ca2+ that spread from the stimulated cell through 2-8 tiers of surrounding cells. During this intercellular Ca2+ wave, cytosolic Ca2+ increased 2- to 12-fold from resting levels of approximately 100 nM. Nanomolar extracellular Ca2+ did not affect the cell-to-cell propagation of the Ca2+ wave, but reduced the magnitude of the cytosolic Ca2+ increases, which was most evident in the mechanically-stimulated cell. Depletion of intracellular Ca2+ stores with thapsigargin eliminated the propagated intercellular Ca2+ wave, but did not prevent the cytosolic Ca2+ increase in the mechanically-stimulated cell, which required extracellular Ca2+ and was attenuated by the addition of the Ca2+ channel blockers Ni2+, Gd3+ and La3+ to the medium. These results are most easily explained by a mechanically-activated channel in the plasma membrane of the stimulated cell. The propagated increase in cytosolic Ca2+ appeared to be communicated to adjacent cells by the passage of an intracellular messenger other than Ca2+ through gap junction channels. However, if the plasma membrane of the mechanically-stimulated cell was ruptured such that there was loss of cytosolic contents, the increase in cytosolic Ca2+ in the surrounding cells was elicited by both a messenger passing through gap junction channels and by a cytosolic factor(s) diffusing through the extracellular medium. These results demonstrate the existence of intercellular Ca2+ signaling in lens cells, which may play a role in regulating cytosolic Ca2+ in the intact lens.

Animals↗
PubMedDate not supplied

Components of astrocytic intercellular calcium signaling.

It has become evident that astrocytes play major roles in central nervous system (CNS) function. Because they are endowed with ion channels, transport pathways, and enzymatic intermediates optimized for ionic uptake, degradation of metabolic products, and inactivation of numerous substances, they are able to sense and correct for changes in neural microenvironment. Besides this housekeeping role, astrocytes modulate neuronal activity either by direct communication through gap junctions or through the release of neurotransmitters and/or nucleotides affecting nearby receptors. One prominent mode by which astrocytes regulate their own activity and influence neuronal behavior is via Ca2+ signals, which may be restricted within one cell or be transmitted throughout the interconnected syncytium through the propagation of intercellular calcium waves. This review aims to outline the most recent advances regarding the active communication of astrocytes that is encoded by intracellular calcium variation.

Adenosine Diphosphate Ribose↗
PubMed1995

Inositol trisphosphate receptor mediated spatiotemporal calcium signalling.

Spatiotemporal Ca2+ signalling in the cytoplasm is currently understood as an excitation phenomenon by analogy with electrical excitation in the plasma membrane. In many cell types, Ca2+ waves and Ca2+ oscillations are mediated by inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ channels in the endoplasmic reticulum membrane, with positive feedback between cytosolic Ca2+ and IP3-induced Ca2+ release creating a regenerative process. Remarkable advances have been made in the past year in the analysis of subcellular Ca2+ microdomains using confocal microscopy and of Ca2+ influx pathways that are functionally coupled to IP3-induced Ca2+ release. Ca2+ signals can be conveyed into the nucleus and mitochondria. Ca2+ entry from outside the cell allows repetitive Ca2+ release by providing Ca2+ to refill the endoplasmic reticulum stores, thus giving rise to frequency-encoded Ca2+ signals.

Animals↗
PubMed2004

Synaptic regulation of the astrocyte calcium signal.

During the last years, a great amount of evidence demonstrates the existence of bidirectional communication between astrocytes and neurons, which has revealed an important active role of astrocytes in the physiology of the nervous system. As a consequence of this evidence, a new concept of the synaptic physiology--"the tripartite synapse"--has been proposed, in which the synapse is formed by three functional elements, i.e., the pre- and postsynaptic elements and the surrounding astrocytes. In this scenario astrocytes play an active role as dynamic regulatory elements in neurotransmission by reciprocally exchanging information with the pre- and postsynaptic elements. The control of the Ca2+ excitability in astrocytes is a key element in this loop of information exchange. In the present article we review and discuss our current knowledge of the properties of the astrocyte intracellular Ca2+ signal and its modulation by the synaptic activity.

Animals↗