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At least 307 records · Page 17Linked to original sources
PubMed2001

Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity.

Information storage in the nervous system requires transcription triggered by synaptically evoked calcium signals. It has been suggested that translocation of calmodulin into the nucleus, initiated by submembranous calcium transients, relays synaptic signals to CREB. Here we show that in hippocampal neurons, signaling to CREB can be activated by nuclear calcium alone and does not require import of cytoplasmic proteins into the nucleus. The nucleus is particularly suited to integrate neuronal firing patterns, and specifies the transcriptional outputs through a burst frequency-to-nuclear calcium amplitude conversion. Calcium release from intracellular stores promotes calcium wave propagation into the nucleus, which is critical for CREB-mediated transcription by synaptic NMDA receptors. Pharmacological or genetic modulation of nuclear calcium may directly affect transcription-dependent memory and cognitive functions.

Animals↗
PubMed2000

Co-expression of calcium signaling components in vertebrate taste bud cells.

In order to investigate the molecular mechanism of calcium signaling pathways common to the vertebrate gustatory systems, we have analyzed the expression of their molecular components. We first identified a phospholipase C (PLC) beta subtype expressed in the taste buds of pond loach (Misgurnus anguillicaudatus), designated DPLCbeta2, which is closely related to mammalian PLCbeta2 shown recently to be expressed in rat taste buds. The taste bud-specific expression of PLCbeta2 in a fish species as well as rat strongly suggests that PLCbeta2 mediates the tastant-induced second messenger response in taste buds, which is common to vertebrates. Next, we examined the correlation of gene expression of the candidate components leading to PLCbeta2 activation in rat circumvallate papillae, including G proteins, G(i2) and gustducin, and a G protein-coupled receptor, TR2. As a result, it was shown that the mRNAs for PLCbeta2 and G(i2) co-exist in the same cells, and PLCbeta2- and G(i2)-positive cells include both gustducin-positive cells and TR2-positive cells. However, no correlation was found between the expressions of TR2 and gustducin as reported previously. Our results thus indicate that a taste transduction pathway comprising TR2, G(i2) and PLCbeta2 occurs in a subset of taste cells.

Animals↗
PubMed2000

Cellular mechanisms of acrolein-induced alteration in calcium signaling in airway smooth muscle.

Acrolein, an unsaturated aliphatic aldehyde, is a potent respiratory irritant. We have previously observed that acrolein administered ex vivo to isolated airways alters subsequent airway responsiveness to muscarinic agonists in terms of both mechanical activity of rings and calcium signaling in isolated cells. In the present study, we have examined the mechanisms by which acrolein alters Ca(2+) signaling. In freshly isolated rat tracheal smooth muscle cells, preexposure to acrolein increased the [Ca(2+)](i) oscillation frequency in response to endothelin 1 (ET-1, 0.1 microM), a contractile agonist that acts via the activation of a receptor different from the muscarinic cholinoceptor. We then studied acrolein-induced alteration in cell signaling with special attention to the steps downstream of membrane receptor activation i.e., the inositol 1,4,5-trisphosphate (InsP(3)) signaling pathway. Pretreatment of cells with LiCl (20 mM), a modulator of InsP(3) concentration, mimicked the effect of acrolein exposure on agonist-induced [Ca(2+)](i) response, i.e., increased the amplitude of the first Ca(2+) rise and the oscillation frequency in response to 0.1 and 10 microM acetylcholine (ACh), respectively. Moreover, in tracheal smooth muscle, preexposure to acrolein significantly increased carbachol-induced [(3)H]inositol-phosphates accumulation, up to 34 +/- 11% above unexposed tissue values. Finally, in beta-escin permeabilized cells, injection of InsP(3) (0.1-10 microM) induced a concentration-dependent [Ca(2+)](i) rise followed, for high InsP(3) concentration, by [Ca(2+)](i) oscillations, a calcium response whose pattern was similar to that induced by ACh. Exposure to acrolein did not alter the InsP(3)-induced [Ca(2+)](i) response. These results indicate that the effect of acrolein exposure on Ca(2+) responses in airway smooth muscle is not restricted to activation of the muscarinic cholinoceptor and is due to an enhancement in agonist-induced InsP(3) production. Since acrolein does not modify InsP(3) receptor channel sensitivity, we conclude that acrolein-induced alteration in calcium signaling can be ascribed to its sole effect on InsP(3) production.

Acrolein↗
PubMed2002

Recovery of deficient cholinergic calcium signaling by adenosine in cultured rat cortical astrocytes.

The regulation of the cholinergic calcium signaling in astroglial cells is thought to play a crucial role in the pathogenesis of Alzheimer's disease. We investigated the action of the cell modulator adenosine on acetylcholine (Ach)-mediated intracellular calcium ([Ca(2+)](i)) transients in cultured rat cortical astrocytes using the Ca(2+) imaging technique. The stable adenosine analog 2-chloroadenosine (2ClA) potentiated the [Ca(2+)](i) rise induced by activation of muscarinic Ach receptors by shifting approximately 30-fold the half-effective Ach concentration. This 2ClA effect was maintained upon removal of extracellular Ca(2+), indicating that Ach-induced [Ca(2+)](i) elevation was due mainly to Ca(2+) mobilization from intracellular stores. Pharmacological studies demonstrated that the 2ClA action was mediated by A1 receptors. Incubation with pertussis toxin abrogated the 2ClA effect but left unchanged the [Ca(2+)](i) rise produced by Ach alone. The [Ca(2+)](i) response elicited by Ach alone was abolished upon blockade of muscarinic receptor subtypes that stimulate phospholipase C, whereas the [Ca(2+)](i) elevation generated by the combined action of subthreshold Ach and 2ClA was not affected. Collectively, these results suggest that the impaired cholinergic signaling, the cardinal symptom of Alzheimer's disease, can be reinforced at the second messenger level by an alternative intracellular Ca(2+) mobilizing path, which can be brought into play by the concomitant activation of A1 purinoceptors and muscarinic receptors negatively coupled to adenylyl cyclase.

2-Chloroadenosine↗
PubMed1997

Endothelin-induced calcium signaling in cultured mouse microglial cells is mediated through ETB receptors.

Microglial cells are the intrinsic immunocompetent cells of the central nervous system, which are activated by brain tissue damage. In this paper we investigated the ability of endothelins (ETs), which are potent vasoconstrictors, to induce intracellular calcium signals in cultured microglia cells. Both endothelin-1 and endothelin-3 increased intracellular Ca2+ concentration ([Ca2+]i). These [Ca2+]i transients were mimicked by BQ3020, an ETB receptor agonist and blocked by BQ788, a selective ETB antagonist, respectively. The calcium signals induced by the endothelins persisted in Ca(2+)-free media. Transcripts encoding the ETB receptor were detected in purified microglial cultures and cDNA fragments derived from ETB receptor mRNA were amplified from 9% of electrophysiologically characterized microglial cells by the use of single-cell RT-PCR.

Animals↗
PubMed1993

A Gq-type G protein couples muscarinic receptors to inositol phosphate and calcium signaling in exocrine cells from the avian salt gland.

Muscarinic acetylcholine receptor (mAChR) activation in isolated cells from the nasal salt gland of the domestic duck (Anas platyrhynchos) results in a rapid increase in the rate of phosphatidylinositol hydrolysis and pronounced intracellular calcium signals. Both responses can be elicited by treating these cells with fluoroaluminate (AlF4-) indicating the involvement of a heterotrimeric G protein in the transmembrane signaling process. To characterize this G protein, electrophoretically separated membrane proteins were blotted onto nitrocellulose filters and probed with peptide-antibodies raised against portions of different alpha-subunits of mammalian G proteins. We could demonstrate the presence of at least four different G proteins in salt gland cell membranes. Two of these proteins (40 and 41 kD) were ADP-ribosylated by pertussis toxin and were recognized by an antiserum against a common sequence in all G protein alpha-subunits. One protein (46 kD) was a cholera toxin-substrate and was recognized by a Gs-specific antiserum; the other (42 kD) was recognized by Gq-specific antisera and was resistant to ADP-ribosylation. Since the initial inositol phosphate production upon receptor activation with carbachol and the resulting calcium signals were not affected by pertussis toxin-pretreatment of salt gland cells, we conclude that muscarinic receptors are coupled to phospholipase C by a Gq-type G protein.

Animals↗
PubMedDate not supplied

Reaction-diffusion equations for simulation of calcium signalling in cell systems.

Numerous experimental and theoretical studies have recently pointed to the importance of calcium signals and their propagation as waves of various kinds inside cells. This phenomenon has been particularly noted in fertilized egg cells. Ca2+ plays a fundamental role in these cells as it is capable of stimulating, by means of a first, large wave, the beginning of an organism's life at fertilization, immediately after sperm penetration. Furthermore, calcium is involved in numerous subsequent processes that are essential for the development of the future embryo, e.g. in contraction of cortical cytoplasm, protein synthesis and cell differentiation. Calcium waves, which are generated by self-oscillating pacemakers and propagate in excitable media, have been observed in some types of egg cells after fertilization. These waves adopt different shapes according to their emission frequency, wavelength, velocity and curvature, and they can occur as solitary waves, target waves or spiral waves. The mathematical models that study the progress of these waves have been developed by means of partial differential equations of the "reaction-diffusion" type. This study will discuss some significant models of intracellular Ca2+ dynamics. Some preliminary considerations will then be made in order to develop a model that describes the propagation of Ca2+ waves in ascidian eggs.

Algorithms↗
PubMed2005

Spatial segregation of neuronal calcium signals encodes different forms of LTP in rat hippocampus.

Calcium regulates numerous processes in the brain. How one signal can coordinate so many diverse actions, even within the same neurone, is the subject of intense investigation. Here we have used two-photon calcium imaging to determine the mechanism that enables calcium to selectively and appropriately induce different forms of long-term potentiation (LTP) in rat hippocampus. Short-lasting LTP (LTP 1) required activation of ryanodine receptors (RyRs), which selectively increased calcium in synaptic spines. LTP of intermediate duration (LTP 2) was dependent on activation of inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) and subsequent calcium release specifically in dendrites. Long-lasting LTP (LTP 3) was selectively dependent on L-type voltage-dependent calcium channels (L-VDCCs), which generated somatic calcium influx. Activation of NMDA receptors was necessary, but not sufficient, for the generation of appropriate calcium signals in spines and dendrites, and the induction of LTP 1 and LTP 2. These results suggest that the selective induction of different forms of LTP is achieved via spatial segregation of functionally distinct calcium signals.

Animals↗
PubMed1993

Inositol trisphosphate and calcium signalling.

Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals. It operates through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle. This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex spatiotemporal patterns of calcium waves and oscillations. Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling.

Animals↗
PubMed1997

Calcium signalling in Arabidopsis thaliana responding to drought and salinity.

Changes in cytosolic free calcium concentration ([Ca2+]cyt) in response to mannitol (drought) and salt treatments were detected in vivo in intact whole Arabidopsis seedlings. Transient elevations of [Ca2+]cyt to around 1.5 microM were observed, and these were substantially inhibited by pretreatment with the calcium-channel blocker lanthanum and to a lesser extent, the calcium-chelator EGTA. The expression of three genes, p5cs, which encodes delta(1)-pyrroline-5-carboxylate synthetase (P5CS), the first enzyme of the proline biosynthesis pathway, rab18 and Iti78 which both encode proteins of unknown function, was induced by mannitol and salt treatments. The induction of all three genes by mannitol was inhibited by pretreatment with lanthanum. Salt-induced p5cs, but not rab18 and Iti78, expression was also inhibited by lanthanum. Induction of p5cs by mannitol was also inhibited by the calcium channel-blockers gadolinium and verapamil and the calcium chelator EGTA, further suggesting the involvement of calcium signalling in this response. Mannitol induced greater levels of p5cs gene expression than an isoosmolar concentration of salt, at both relatively high and low concentrations. However, calcium transients were of a similar magnitude and duration in response to both mannitol and isoosmolar concentrations of salt, suggesting that a factor other than calcium is involved in the discrimination between drought and salinity signals in Arabidopsis. In order to gauge the involvement of the vacuole as an intracellular calcium store in the response of Arabidopsis to mannitol, [Ca2+]cyt was measured at the microdomain adjacent to the vacuolar membrane. The results obtained were consistent with a significant calcium release from the vacuole contributing to the overall mannitol-induced [Ca2+]cyt response. Data obtained by using inhibitors of inositol signalling suggested that this release was occurring through IP3-dependent calcium channels.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed1993

[Regulation of intracellular calcium signaling in cardiac muscle].

beta-Adrenoceptor stimulation decreases the calcium-sensitivity of cardiac contractile proteins through cAMP-dependent phosphorylation of troponin I and others. Agents such as alpha 1-adrenergic receptor agonists, endothelin, angiotensin II et al. that stimulate PI turnover elicit positive inotropic responses associated with increase in the calcium-sensitivity. Phorbol ester decreases the apparent sensitivity of the contractile proteins to calcium ion through the phosphorylation of troponin T and others. Myocardial contractile force may be altered by increasing or decreasing the calcium responsiveness of the myofilaments by various drugs, which change the calcium affinity of calcium-binding proteins such as troponin C and calmodulin. Moreover, we isolated a new calcium-binding protein (S100C) from porcine heart and cloned the cDNA for this protein. Modulation of intracellular calcium signaling in cardiac muscle by protein phosphorylation and drugs awaits further investigation.

Amino Acid Sequence↗
PubMed1995

Calcium signaling in neurons: molecular mechanisms and cellular consequences.

Neuronal activity can lead to marked increases in the concentration of cytosolic calcium, which then functions as a second messenger that mediates a wide range of cellular responses. Calcium binds to calmodulin and stimulates the activity of a variety of enzymes, including calcium-calmodulin kinases and calcium-sensitive adenylate cyclases. These enzymes transduce the calcium signal and effect short-term biological responses, such as the modification of synaptic proteins and long-lasting neuronal responses that require changes in gene expression. Recent studies of calcium signal-transduction mechanisms have revealed that, depending on the route of entry into a neuron, calcium differentially affects processes that are central to the development and plasticity of the nervous system, including activity-dependent cell survival, modulation of synaptic strength, and calcium-mediated cell death.

Animals↗
PubMed2005

Modeling and analysis of calcium signaling events leading to long-term depression in cerebellar Purkinje cells.

Modeling and simulation of the calcium signaling events that precede long-term depression of synaptic activity in cerebellar Purkinje cells are performed using the Virtual Cell biological modeling framework. It is found that the unusually high density and low sensitivity of inositol-1,4,5-trisphosphate receptors (IP3R) are critical to the ability of the cell to generate and localize a calcium spike in a single dendritic spine. The results also demonstrate the model's capability to simulate the supralinear calcium spike observed experimentally during coincident activation of the parallel and climbing fibers. The sensitivity of the calcium spikes to certain biological and geometrical effects is investigated as well as the mechanisms that underlie the cell's ability to generate the supralinear spike. The sensitivity of calcium release rates from the IP3R to calcium concentrations, as well as IP3 concentrations, allows the calcium spike to form. The diffusion barrier caused by the small radius of the spine neck is shown to be important, as a threshold radius is observed above which a spike cannot be formed. Additionally, the calcium buffer capacity and diffusion rates from the spine are found to be important parameters in shaping the calcium spike.

Adaptation, Physiological↗
PubMed2001

Calcium signaling by HBx protein in hepatitis B virus DNA replication.

Hepatitis B virus (HBV) infects more than 300 million people and is a leading cause of liver cancer and disease. The HBV HBx protein is essential for infection; HBx activation of Src is important for HBV DNA replication. In our study, HBx activated cytosolic calcium-dependent proline-rich tyrosine kinase-2 (Pyk2), a Src kinase activator. HBx activation of HBV DNA replication was blocked by inhibiting Pyk2 or calcium signaling mediated by mitochondrial calcium channels, which suggests that HBx targets mitochondrial calcium regulation. Reagents that increased cytosolic calcium substituted for HBx protein in HBV DNA replication. Thus, alteration of cytosolic calcium was a fundamental requirement for HBV replication and was mediated by HBx protein.

Calcium↗
PubMed2006

Tastants evoke cAMP signal in taste buds that is independent of calcium signaling.

We previously showed that rat taste buds express several adenylyl cyclases (ACs) of which only AC8 is known to be stimulated by Ca2+. Here we demonstrate by direct measurements of cAMP levels that AC activity in taste buds is stimulated by treatments that elevate intracellular Ca2+. Specifically, 5 microM thapsigargin or 3 microM A-23187 (calcium ionophore), both of which increase intracellular Ca2+ concentration ([Ca2+]i), lead to a significant elevation of cAMP levels. This calcium stimulation of AC activity requires extracellular Ca2+, suggesting that it is dependent on Ca2+ entry rather than release from stores. With immunofluorescence microscopy, we show that the calcium-stimulated AC8 is principally expressed in taste cells that also express phospholipase Cbeta2 (i.e., cells that elevate [Ca2+]i in response to sweet, bitter, or umami stimuli). Taste transduction for sucrose is known to result in an elevation of both cAMP and calcium in taste buds. Thus we tested whether the cAMP increase in response to sucrose is a downstream consequence of calcium elevation. Even under conditions of depletion of stored and extracellular calcium, the cAMP response to sucrose stimulation persists in taste cells. The cAMP signal in response to monosodium glutamate stimulation is similarly unperturbed by calcium depletion. Our results suggest that tastant-evoked cAMP signals are not simply a secondary consequence of calcium modulation. Instead, cAMP and released Ca2+ may represent independent second messenger signals downstream of taste receptors.

Animals↗
PubMed1997

Calcium signaling in prostate cancer cells: evidence for multiple receptors and enhanced sensitivity to bombesin/GRP.

BACKGROUND: Cellular calcium is an important second messenger for growth regulation. We sought to identify potentially important receptors on prostate tumor cells by screening over 20 agonists for their ability to increase intracellular free calcium ([Ca2+]i) in several human prostate tumor cell lines. METHODS: Intracellular calcium mobilization was detected using fura-2. RESULTS: We found bombesin, GRP, ATP/UTP, lysophosphatidic acid, thrombin, endothelin, histamine, and bradykinin increased [Ca2+]i in the advanced tumor cell lines DU-145, PC3, and PPC-1. Bombesin failed to elevate [Ca2+]i in an immortalized human prostate cell line. Rank-order of potency studies suggested the presence of P2U nucleotide receptors for ATP/UTP on prostate epithelial cells. Potency studies also revealed GRP > > bombesin > > neuromedin B at elevating [Ca2+]i in responding tumor cells. CONCLUSIONS: These findings indicate that androgen independent prostate tumor cell lines express multiple receptors capable of elevating intracellular calcium, and suggest that GRP receptors may be selectively expressed and/or coupled to calcium signaling during prostate tumor progression. Calcium sensitive cellular events may therefore contribute to the progression of prostate cancer.

Bombesin↗
PubMed1995

Synaptic differentiation of a single motor neuron: conjoint definition of transmitter release, presynaptic calcium signals, and ultrastructure.

The opener muscle in the walking legs of the crayfish (Procambarus clarkii) is innervated by only one excitatory motor neuron, yet excitatory postsynaptic potentials (EPSPs) of proximal fibers are eightfold larger than those of central muscle fibers at low frequencies of activation, due in large measure to differences in presynaptic properties. We investigated quantal release properties, calcium signals, and ultrastructure of presynaptic terminals to elucidate factors that could account for the physiological differences. Focal macropatch electrodes were placed over individual visualized terminal varicosities to obtain records of quantal contributions to the excitatory junctional current (EJC). At low frequencies of activation, mean quantal content is greater for proximal than for central varicosities. This difference is due to a higher probability of release per synapse, and not to a larger number of active synapses. Recorded varicosities were labeled with fluorescent beads deposited by the electrode. These beads adhered to the muscle fibers, outlining the recorded site for subsequent serial thin sectioning and reconstruction from electron micrographs. Comparisons of structure and function were made for individual varicosities. The number of active zones per terminal surface area and the number of synapses with multiple active zones (complex synapses) were greater in high-output varicosities. Calcium indicators were loaded into proximal and central nerve terminals by axonal injection to compare the relative differences in calcium buildup during stimulation. Presynaptic calcium signals were larger for proximal varicosities than for central varicosities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Calcium signaling in airway smooth muscle cells is altered by in vitro exposure to the aldehyde acrolein.

We have previously observed that acrolein administered ex vivo to isolated airways alters the subsequent airway responsiveness. To examine the cellular mechanisms involved in this alteration, we have studied the effect of acrolein exposure on calcium signaling in myocytes freshly isolated from rat trachea. We have also studied the effect of acrolein exposure on isometric contraction of rat epithelium-free tracheal rings. Tissues were exposed to a variety of acrolein concentrations from 0.1 to 1 microM and durations from 5 to 15 min. In isolated cells, exposure to acrolein did not modify the resting cytosolic Ca2+ concentration ([Ca2+]i) whatever the concentration or duration of exposure, but altered the pattern of the Ca2+ response to acetylcholine (ACh). ACh typically induces an initial [Ca2+]i rise followed by peaks of decreasing amplitude (oscillations). Exposure to a fixed concentration of acrolein (0.2 microM) for 5 and 10 min significantly enhanced the amplitude of the initial [Ca2+]i rise in response to a low concentration of ACh (0.1 microM) by 50.8 and 77%, respectively. Similarly, exposure for a fixed duration of 10 min significantly enhanced the amplitude of the initial [Ca2+]i rise by 49.4% at an acrolein concentration of 0.3 microM. When cells were stimulated with a high ACh concentration (10 microM), the value of the first [Ca2+]i peak was not changed by acrolein exposure; but the frequency at which subsequent peaks occurred was significantly increased by 44.4% after 10 min of exposure to a fixed concentration of 0.2 microM and by 36.3% following an exposure for a fixed duration of 10 min at the concentration of 0.3 microM. In contrast, acrolein, whatever the concentration, had no effect on the caffeine-induced [Ca2+]i response. In rat epithelium-free tracheal rings, acrolein increased the response to muscarinic stimulation, with a maximal effect observed for an exposure to 0.3 microM for 10 min. The effect of acrolein on the [Ca2+]i response of isolated myocytes occurred over a range of doses similar to that on the contractile response of rings, suggesting that the effect of this pollutant on calcium signaling may account, at least partially, for acrolein-induced airway hyperresponsiveness.

Acetylcholine↗