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At least 37 records · Page 2Linked to original sources
PubMed2006

Movement of calcium signals and calcium-binding proteins: firewalls, traps and tunnels.

In the board game 'Snakes and Ladders', placed on the image of a pancreatic acinar cell, calcium ions have to move from release sites in the secretory region to the nucleus. There is another important contraflow - from calcium entry channels in the basal part of the cell to ER (endoplasmic reticulum) terminals in the secretory granule region. Both transport routes are perilous as the messenger can disappear in any place on the game board. It can be grabbed by calcium ATPases of the ER (masquerading as a snake but functioning like a ladder) and tunnelled through its low buffering environment, it can be lured into the whirlpools of mitochondria uniporters and forced to regulate the tricarboxylic acid cycle, and it can be permanently placed inside the matrix of secretory granules and released only outside the cell. The organelles could trade calcium (e.g. from the ER to mitochondria and vice versa) almost depriving this ion the light of the cytosol and noble company of cytosolic calcium buffers. Altogether it is a rich and colourful story.

Animals↗
PubMed2005

Use of transgenic zebrafish reporter lines to study calcium signalling in development.

Calcium signals are associated with many of the events common to animal development. Understanding the role of these calcium signals requires the ability to visualise and manipulate calcium levels in the developing embryo. Recent work has led to the development of sensitive protein-based probes that can be used to generate transgenic animals for the analysis of calcium signalling in vivo. This paper focuses on the use of genetically encoded calcium probes to follow calcium signals in zebrafish. It reviews progress and speculates on the potential for use in the future.

Animals↗
PubMed2004

New aspects of nuclear calcium signalling.

Nuclear calcium signalling has been a controversial battlefield for many years and the question of how permeable the nuclear pore complexes (NPCs) are to Ca2+ has been the subject of a particularly hot dispute. Recent data from isolated nuclei suggest that the NPCs are open even after depletion of the Ca2+ store in the nuclear envelope. Other research has suggested that a new Ca2+ -releasing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP), can liberate Ca2+ only from acidic organelles, probably lysosomes, rather than from the traditional Ca2+ store in the endoplasmic reticulum (ER). Recent work indicates that NAADP can release Ca2+ from the nuclear envelope (NE), which has a thapsigargin-sensitive, ER-type Ca2+ store. NAADP acts in a manner similar to inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] or cyclic ADP-ribose (cADPR): all three messengers are equally able to reduce the Ca2+ concentration inside the NE and this is associated with a transient rise in the nucleoplasmic Ca2+ concentration. The NE contains ryanodine receptors (RyRs) and Ins(1,4,5)P3 receptors [Ins(1,4,5)P3Rs], and these can be activated separately and independently: the RyRs by either NAADP or cADPR, and the Ins(1,4,5)P3Rs by Ins(1,4,5)P3.

Animals↗
PubMedDate not supplied

Mechanisms controlling gene expression by nuclear calcium signals.

Nuclear calcium is an important regulator of gene expression following membrane depolarisation of electrically excitable cells. Here we describe nuclear calcium transients in hippocampal neurons following activation of calcium influx through L-type voltage-sensitive calcium channels and N-methyl-D-aspartate (NMDA) receptors, as well as following calcium release from intracellular caffeine-sensitive stores. Increases in nuclear calcium activate gene transcription by a mechanism that is distinct from gene regulation by cytoplasmic calcium signals and involves the cAMP response element (CRE) and the CRE binding protein, CREB. The nuclear calcium/calmodulin dependent (CaM) protein kinase IV, which is expressed in cultured hippocampal neurons and in the mouse pituitary cell line AtT20, may function as a mediator of nuclear calcium-induced transcription.

Animals↗
PubMed1999

Localized intracellular calcium signaling in muscle: calcium sparks and calcium quarks.

Subcellularly localized Ca2+ signals in cardiac and skeletal muscle have recently been identified as elementary Ca2+ signaling events. The signals, termed Ca2+ sparks and Ca2+ quarks, represent openings of Ca2+ release channels located in the membrane of the sarcoplasmic reticulum (SR). In cardiac muscle, the revolutionary discovery of Ca2+ sparks has allowed the development of a fundamentally different concept for the amplification of Ca2+ signals by Ca(2+)-induced Ca2+ release. In such a system, a graded amplification of the triggering Ca2+ signal entering the myocyte via L-type Ca2+ channels is accomplished by a recruitment process whereby individual SR Ca2+ release units are locally controlled by L-type Ca2+ channels. In skeletal muscle, the initial SR Ca2+ release is governed by voltage-sensors but subsequently activates additional Ca2+ sparks by Ca(2+)-induced Ca2+ release from the SR. Results from studies on elementary Ca2+ release events will improve our knowledge of muscle Ca2+ signaling at all levels of complexity, from the molecule to normal cellular function, and from the regulation of cardiac and skeletal muscle force to the pathophysiology of excitation-contraction coupling.

Animals↗
PubMed2002

Hypochlorous acid activates tyrosine phosphorylation signal pathways leading to calcium signaling and TNFalpha production.

Hypochlorous acid is an important oxidizing agent produced by neutrophils to aid in defense against pathogens. Although hypochlorous acid is known to cause tissue damage due to its cytotoxicity, the effect of this oxidizing agent on signal transduction by cells of the immune system and its effects on their responses are not well understood. In this study, hypochlorous acid was found to induce cellular tyrosine phosphorylation in both T and B lymphocytes, activate the ZAP-70 tyrosine kinase, and induce cellular calcium signaling in a tyrosine kinase-dependent manner. These signaling events also occurred in T cell lines that did not express the T-cell receptor, indicating the ability of hypochlorous acid to bypass normal receptor control. Hypochlorous acid induced tumor necrosis factor-alpha production in peripheral blood mononuclear cells in a tyrosine kinase-dependent manner. These results suggest that hypochlorous acid may contribute to inflammatory responses by activating signal pathways in cells of the immune system.

Calcium Signaling↗
PubMed2004

Integration and channeling of calcium signaling through the CBL calcium sensor/CIPK protein kinase network.

Plant development and reproduction depend on a precise recognition of environmental conditions and the integration of this information with endogenous metabolic and developmental cues. Calcium ions have been firmly established as ubiquitous second messengers functioning in these processes. Calcium signal deciphering and signal-response coupling often involve calcium-binding proteins as responders or relays in this information flow. Here we review the calcineurin B-like protein (CBL) calcium sensor/CBL-interacting protein kinase (CIPK) network as a newly emerging signaling system mediating a complex array of environmental stimuli. We focus particularly on the mechanisms generating signaling specificity. Moreover, we emphasize the functional implications that are emerging from the analyses of CBL and CIPK loss-of-function mutants.

Calcium↗
PubMed2002

Analytic description of stochastic calcium-signaling periodicity.

Calcium release is an important tool for cellular signaling processes where chemical signals are converted into spatio-temporal variations of intracellular calcium concentration. We investigated the temporal behavior of a single cluster of inositol-(1,4,5)-triphosphate receptor (IP3R)-I channels and will present an analytic approach to obtain the spectrum of the calcium signal within the cluster. We compare these results with stochastic simulations and obtain an intermediate number of channels per cluster for optimal signaling periodicity.

Biophysical Phenomena↗
PubMed2002

Calcium signaling between sarcolemmal calcium channels and ryanodine receptors in heart cells.

Cardiac excitation-Ca2+ release coupling is, in essence, a tale of two molecules, sarcolemmal voltage-gated L-type Ca2+ channels (LCCs) and intracellular ryanodine receptors (RyRs), communicating via the Ca2+-induced Ca2+ release mechanism. Recent advances have provided a microscopic view of the intermolecular Ca2+ signaling between LCCs and RyRs. In a dyadic junction or a "couplon", LCCs open and close stochastically upon depolarization, delivering a train of high local Ca2+ pulses ("Ca2+ sparklets") to the RyRs in the abutting SR terminal cisternae. Stochastic activation of RyRs discharges "Ca2+ sparks" from different couplons, which summate into global Ca2+ transients. Hence, ignition of Ca2+ sparks by Ca2+ sparklets constitute elementary events of EC coupling. While the sparklet-spark coupling is of low fidelity (at 0 mV, about one out of 50 sparklets triggers a spark under physiological conditions), the high-gain amplification of CICR (approximately 15 at 0 mV) is achieved because of the greater single-channel flux and open time of RyRs and multi-RyR origin of Ca2+ spark. The global stability of CICR is safeguarded by many factors acting in synergy, including physical separation of RyR clusters, sheer Ca2+ gradients around the channel pores, low intrinsic Ca2+ sensitivity of RyRs in vivo, and high cooperativity for the Ca2+-dependent spark activation. The local stability of CICR is insured because of strong, use-dependent inactivation of RyRs, that terminates Ca2+ sparks and confers persistent local SR refractoriness.

Animals↗
PubMed1994

Localization of calcium signals by a mobile calcium buffer in frog saccular hair cells.

A recent study (Roberts, 1993) of saccular hair cells from grass frogs (Rana pipiens) has suggested a mechanism by which the unusually high concentrations of calcium-binding proteins found in certain sensory receptors and neurons, particularly in the auditory system, can influence short-range intracellular calcium signaling. In frog saccular hair cells, the mechanism operates within arrays of calcium channels and calcium-activated potassium channels that are involved in the cells' electrical resonance and synaptic transmission. The present study tests the hypothesis that calbindin-D28k, one of the most abundant proteins in these cells, can serve as a mobile calcium buffer that reduces and localizes changes in the intracellular free-calcium concentration ([Ca2+]i) by shuttling calcium away from the channel arrays. Based upon theoretical analysis and computer modeling, it is shown that [Ca2+]i near one or more open channels quickly reaches a steady-state level determined primarily by two properties of the buffer, the mean time (tau c) before it captures a free-calcium ion and a replenishment factor (R), which are related to the buffer's diffusional mobility (DBu), association rate constant (kon), and concentration (Bo) by tau c = (konB0)-1 and R = B0DBu. Simulation of calcium entry through a channel array showed that approximately 1.5 mM of a molecule with the diffusional and binding properties expected for calbindin-D28k (Bo approximately 8 mM calcium-binding sites) is needed to reproduce the previous experimental results. A lower concentration (B0 = 2 mM) was almost completely depleted within the channel array by a modest calcium current (8 pA = 12% of calcium channels open), but still had two important effects: it caused [Ca2+]i to fall steeply with distance outside the array (space constant < 50 nm), and returned [Ca2+]i quickly to the resting level after the channels closed. A high concentration of calbindin-D28k can thus influence the cell's electrical resonance and synaptic transmission. Its most important functions may be to localize regions of high [Ca2+]i and speed the return of [Ca2+]i toward the resting level.

Animals↗
PubMed1997

Role of the cytoskeleton in calcium signaling in NIH 3T3 cells. An intact cytoskeleton is required for agonist-induced [Ca2+]i signaling, but not for capacitative calcium entry.

Treatment of NIH 3T3 cells with cytochalasin D (10 microM, 1 h at 37 degrees C) disrupted the actin cytoskeleton and changed the cells from a planar, extended morphology, to a rounded shape. Calcium mobilization by ATP or by platelet-derived growth factor was abolished, while the ability of thapsigargin (2 microM) to empty calcium stores and activate calcium influx was unaffected. Similar experiments with nocodazole to depolymerize the tubulin network yielded identical results. Platelet-derived growth factor induced an increase in inositol phosphates, and this increase was undiminished in the presence of cytochalasin D. Therefore, the blockade of agonist responses by this drug does not result from decreased phospholipase C. Injection of inositol 1,4,5-trisphosphate (IP3) released calcium to the same extent in control and cytochalasin D-treated cells. Confocal microscopic studies revealed a significant rearrangement of the endoplasmic reticulum after cytochalasin D treatment. Thus, disruption of the cytoskeleton blocks agonist-elicited [Ca2+]i mobilization, but this effect does not result from a lower calcium storage capacity, impaired function of the IP3 receptor, or diminished phospholipase C activity. We suggest that cytoskeletal disruption alters the spatial relationship between phospholipase C and IP3 receptors, impairing phospholipase C-dependent calcium signaling. Capacitative calcium entry was not altered under these conditions, indicating that the coupling between depletion of intracellular calcium stores and calcium entry does not depend on a precise structural relationship between intracellular stores and plasma membrane calcium channels.

3T3 Cells↗
PubMedDate not supplied

Calcium signalling in glial cells.

Calcium signals are the universal way of glial responses to the various types of stimulation. Glial cells express numerous receptors and ion channels linked to the generation of complex cytoplasmic calcium responses. The glial calcium signals are able to propagate within glial cells and to create a spreading intercellular Ca2+ wave which allow information exchange within the glial networks. These propagating Ca2+ waves are primarily mediated by intracellular excitable media formed by intracellular calcium storage organelles. The glial calcium signals could be evoked by neuronal activity and vice versa they may initiate electrical and Ca2+ responses in adjacent neurones. Thus glial calcium signals could integrate glial and neuronal compartments being therefore involved in the information processing in the brain.

Animals↗
PubMed2000

Ruled by waves? Intracellular and intercellular calcium signalling.

The field of calcium signalling has evolved rapidly the last 20 years. Physiologists had worked with cytosolic Ca2+ as the coupler of excitation and contraction of muscles and as a secretory signal in exocrine glands and in the synapses of the brain for several decades before the discovery of cellular calcium as a second messenger. Development of powerful techniques for measuring the concentration of cytosolic free calcium ions in cell suspensions and later in single cells and even in different cellular compartments, has resulted in an upsurge in the knowledge of the cellular machinery involved in intracellular calcium signalling. However, the focus on intracellular mechanisms might have led this field of study away from physiology. During the last few years there is an increasing evidence for an important role of calcium also as an intercellular signal. Via gap junctions calcium is able to co-ordinate cell populations and even organs like the liver. Here we will give an overview of the general mechanisms of intracellular calcium signalling, and then review the recent data on intercellular calcium signals. A functional coupling of cells in different tissues and organs by the way of calcium might be an important mechanism for controlling and synchronizing physiological responses

Animals↗
PubMed2000

Dendritic spikes and their influence on extracellular calcium signaling.

Extracellular calcium is critical for many neural functions, including neurotransmission, cell adhesion, and neural plasticity. Experiments have shown that normal neural activity is associated with changes in extracellular calcium, which has motivated recent computational work that employs such fluctuations in an information-bearing role. This possibility suggests that a new style of computing is taking place in the mammalian brain in addition to current 'circuit' models that use only neurons and connections. Previous computational models of rapid external calcium changes used only rough approximations of calcium channel dynamics to compute the expected calcium decrements in the extracellular space. Using realistic calcium channel models, experimentally measured back-propagating action potentials, and a model of the extracellular space, we computed the fluctuations in external calcium that accrue during neural activity. In this realistic setting, we showed that rapid, significant changes in local external calcium can occur when dendrites are invaded by back-propagating spikes, even in the presence of an extracellular calcium buffer. We further showed how different geometric arrangements of calcium channels or dendrites prolong or amplify these fluctuations. Finally, we computed the influence of experimentally measured synaptic input on peridendritic calcium fluctuations. Remarkably, appropriately timed synaptic input can amplify significantly the decrement in external calcium. The model shows that the extracellular space and the calcium channels that access it provide a medium that naturally integrates coincident spike activity from different dendrites that intersect the same tissue volume.

Algorithms↗
PubMed2005

S100A9 deficiency alters adenosine-5'-triphosphate induced calcium signalling but does not generally interfere with calcium and zinc homeostasis in murine neutrophils.

The two calcium- and zinc-binding proteins, S100A9 and S100 A8, abundant in myeloid cells are considered to play important roles in both calcium signalling and zinc homeostasis. Polymorphonuclear neutrophils from S100A9 ko mice are also devoid of S100A8. Therefore, S100A9-deficient neutrophils were used as a model to study the role of the two S100 proteins in the neutrophils's calcium and zinc metabolism. Analysis of the intracellular zinc level upon pyrithione and (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide (NOR-1) treatment revealed no differences between S100A9-deficient and wildtype neutrophils. Similar, the calcium signals were not distinguishable from S100A9-deficient and wildtype neutrophils upon stimulation with platelet activating factor (PAF), thapsigargin or macrophage inflammatory protein 1 alpha (MIP-1 alpha), indicating despite their massive expression S100A8/A9 do neither serve as calcium nor as zinc buffering proteins in granulocytes. In contrast, stimulation with adenosine-5'-triphosphate (ATP) induces a significant stronger increase of the intracellular free calcium level in S100A9-deficient cells compared to wildtype cells. Moreover, the ATP-induced calcium signal was still different when the cells were incubated in calcium free buffer suggesting that pirinergic receptors of the P(2Y) class could be involved in this signalling pathway.

Adenosine Triphosphate↗
PubMed2002

Calcium signal compartmentalization.

Cytosolic calcium signals are produced by suddenly increasing the concentration of free calcium ions (Ca2+). This can occur by opening channels permeable to Ca2+ either in the surface cell membrane or in the membranes of intracellular organelles containing high Ca2+ concentrations. Ca2+ signals can control several different processes, even in the same cell. In pancreatic acinar cells, for example, Ca2+ signals do not only control the normal secretion of digestive enzymes, but can also activate autodigestion and programmed cell death. Recent technical advances have shown that different patterns of Ca2+ signals can be created, in space and time, which allow specific cellular responses to be elicited. The mechanisms responsible for Ca2+ signal compartmentalization are now largely known and will be described on the basis of recent studies of Ca2+ transport pathways and their regulation in pancreatic acinar cells. It turns out that the Ca2+ handling as well as the structural characteristics of the endoplasmic reticulum (ER) and the mitochondria are of particular importance. Using a variety of Ca(2+)-sensitive fluorescent probes placed in different sub-cellular compartments in combination with local uncaging of caged Ca2+, many new insights into Ca2+ signal generation, compartmentalization and termination have recently been obtained.

Animals↗