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Journal ArticleDOI

Elementary and global aspects of calcium signalling.

01 Mar 1997-The Journal of Physiology (Wiley/Blackwell (10.1111))-Vol. 499, Iss: 2, pp 291-306
TL;DR: Using Ca2+ imaging techniques, the opening of individual channels has now been visualized and models have been proposed to explain how these elementary events are coordinated to generate the global Ca 2+ signals that regulate cellular activity.
Abstract: Calcium is a ubiquitous second messenger used to regulate a wide range of cellular processes. This role in signalling has to be conducted against the rigid homeostatic mechanisms that ensure that the resting level of Ca2+ is kept low (i.e. between 20 and 100 nmol l-1) in order to avoid the cytotoxic effects of a prolonged elevation of [Ca2+]. Cells have evolved a sophisticated signalling system based on the generation of brief pulses of Ca2+ which enables this ion to be used as a messenger, thus avoiding its toxic effects. Such Ca2+ spikes usually result from the coordinated release of Ca2+ from internal stores using either inositol 1,4,5-trisphosphate or ryanodine receptors. Using Ca2+ imaging techniques, the opening of individual channels has now been visualized and models have been proposed to explain how these elementary events are coordinated to generate the global Ca2+ signals that regulate cellular activity.
Citations
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Journal ArticleDOI
TL;DR: The universality of calcium as an intracellular messenger depends on its enormous versatility, which is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion.
Abstract: The universality of calcium as an intracellular messenger depends on its enormous versatility. Cells have a calcium signalling toolkit with many components that can be mixed and matched to create a wide range of spatial and temporal signals. This versatility is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion, and must be accomplished within the context of calcium being highly toxic. Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis.

5,369 citations


Cites background from "Elementary and global aspects of ca..."

  • ...Further versatility is achieved by varying the spatial and temporal aspects of Ca 2+ signallin...

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Journal ArticleDOI
01 Jul 1998-Neuron
TL;DR: This work was supported by a grant from the European Commission BIOMED2 (BMH4-CT96-0656) and has been endorsed by the Food and Drug Administration (FDA) for use in clinical practice.

2,059 citations


Cites background from "Elementary and global aspects of ca..."

  • ...The existence of such Ca21events (Bootman and Berridge 1995; Berridge, 1997; waves is very dependent on the progressive loading ofLipp and Niggli, 1997)....

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  • ...…the subsurfacein cardiac cells, in that Ca21 entering through voltage- operated channels triggers RYR2s to release internal cisternae have much in common with the triadic junctions in muscle and may thus be responsible for theCa21 through a process of Ca21-induced Ca21 release (Berridge, 1997)....

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Journal ArticleDOI
TL;DR: Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation.
Abstract: The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+ into the cytoplasm in response to InsP3 produced by diverse stimuli, generating complex local and global Ca2+ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R.

1,093 citations

Journal ArticleDOI
TL;DR: The endoplasmic reticulum is a multifunctional signaling organelle that controls a wide range of cellular processes such as the entry and release of Ca(2+), sterol biosynthesis, apoptosis and the release of arachidonic acid.

904 citations

Journal ArticleDOI
TL;DR: Both structural and pigmentation mutants deteriorated faster than the wild types during natural aging at room temperature, with structural mutants being the most strongly affected.
Abstract: The testa of higher plant seeds protects the embryo against adverse environmental conditions. Its role is assumed mainly by controlling germination through dormancy imposition and by limiting the detrimental activity of physical and biological agents during seed storage. To analyze the function of the testa in the model plant Arabidopsis, we compared mutants affected in testa pigmentation and/or structure for dormancy, germination, and storability. The seeds of most mutants exhibited reduced dormancy. Moreover, unlike wild-type testas, mutant testas were permeable to tetrazolium salts. These altered dormancy and tetrazolium uptake properties were related to defects in the pigmentation of the endothelium and its neighboring crushed parenchymatic layers, as determined by vanillin staining and microscopic observations. Structural aberrations such as missing layers or a modified epidermal layer in specific mutants also affected dormancy levels and permeability to tetrazolium. Both structural and pigmentation mutants deteriorated faster than the wild types during natural aging at room temperature, with structural mutants being the most strongly affected.

786 citations

References
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Journal ArticleDOI
28 Jan 1993-Nature
TL;DR: Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle.
Abstract: 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.

6,389 citations


"Elementary and global aspects of ca..." refers background in this paper

  • ...In order to overcome the twin problems of an inherent cytotoxicity and low diffusibility, cells have evolved an ingenious mechanism of signalling based on presenting Ca2+ as brief spikes often organized as regenerative waves (Cheek, 1991; Berridge, 1993; Clapham, 1995)....

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  • ...In most cells, it is the internal stores which provide most of the signal Ca2+ so attention has focused on the intracellular Ca2+ channels, of which there are two main types (Berridge, 1993; Clapham, 1995)....

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  • ...In most cells, it is the internal stores which provide most of the signal Ca 2+ so attention has focused on the intracellular Ca 2+ channels, of which there are two main types (Berridge, 1993; Clapham, 1995)....

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Journal ArticleDOI
01 Nov 1984-Nature
TL;DR: Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.
Abstract: There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

5,712 citations

Journal ArticleDOI
TL;DR: A capacitative model is proposed for the mechanism by which activation of surface membrane receptors causes sustained Ca2+ entry into cells from the extracellular space, which allows forCa2+ release and Ca2-mobilization to be controlled by a single messenger, inositol (1,4,5) trisphosphate.

2,482 citations

Journal ArticleDOI
03 Nov 1983-Nature
TL;DR: It is reported here that micromolar concentrations of Ins1,4,5P3 release Ca2+ from a nonmitochondrial intracellular Ca2- store in pancreatic acinar cells, and the results strongly suggest that this is the same Ca1+ store that is released by acetylcholine.
Abstract: Activation of receptors for a wide variety of hormones and neurotransmitters leads to an increase in the intracellular level of calcium. Much of this calcium is released from intracellular stores but the link between surface receptors and this internal calcium reservoir is unknown. Hydrolysis of the phosphoinositides, which is another characteristic feature of these receptors, has been implicated in calcium mobilization. The primary lipid substrates for the receptor mechanism seem to be two polyphosphoinositides, phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P2), which are rapidly hydrolysed following receptor activation in various cells and tissues. The action of phospholipase C on these polyphosphoinositides results in the rapid formation of the water-soluble products inositol 1,4-bisphosphate (Ins1,4P2) and inositol 1,4,5-trisphosphate (Ins1,4,5P3). In the insect salivary gland, where changes in Ins1,4P2 and Ins1,4,5P2 have been studied at early time periods, increases in these inositol phosphates are sufficiently rapid to suggest that they might mobilize internal calcium. We report here that micromolar concentrations of Ins1,4,5P3 release Ca2+ from a nonmitochondrial intracellular Ca2+ store in pancreatic acinar cells. Our results strongly suggest that this is the same Ca2+ store that is released by acetylcholine.

2,434 citations

Journal ArticleDOI
29 Oct 1993-Science
TL;DR: The calcium spark is the consequence of elementary events underlying excitation-contraction coupling and provides an explanation for both spontaneous and triggered changes in the intracellular calcium concentration in the mammalian heart.
Abstract: Spontaneous local increases in the concentration of intracellular calcium, called "calcium sparks," were detected in quiescent rat heart cells with a laser scanning confocal microscope and the fluorescent calcium indicator fluo-3 Estimates of calcium flux associated with the sparks suggest that calcium sparks result from spontaneous openings of single sarcoplasmic reticulum (SR) calcium-release channels, a finding supported by ryanodine-dependent changes of spark kinetics At resting intracellular calcium concentrations, these SR calcium-release channels had a low rate of opening (approximately 00001 per second) An increase in the calcium content of the SR, however, was associated with a fourfold increase in opening rate and resulted in some sparks triggering propagating waves of increased intracellular calcium concentration The calcium spark is the consequence of elementary events underlying excitation-contraction coupling and provides an explanation for both spontaneous and triggered changes in the intracellular calcium concentration in the mammalian heart

1,913 citations


"Elementary and global aspects of ca..." refers background in this paper

  • ...Ca2+ imaging has revealed that these units can fire spontaneously and independently of each other to produce sparks which fail to activate neighbouring units because of their low Ca2+ sensitivities (Cheng et al. 1993; Lopez-Lopez et al. 1995; Cannell et al. 1995)....

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  • ...The brief opening of these channels gives rise to localized pulses (approximately 2 µm in diameter) such as the sparks in cardiac muscle (Cheng et al. 1993) or the blips and puffs in Xenopus oocytes (Yao et al. 1995; Parker and Yao, 1996)....

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  • ...In effect, this Ca2+ overload converts the cytoplasm into an excitable medium such that a Ca2+ spark can ignite neighbouring units, thereby setting up a regenerative Ca2+ wave (Cheng et al. 1993)....

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