Pulsatile intracellular calcium release does not depend on fluctuations in inositol trisphosphate concentration

Wakui, Makoto; Potter, Barry V. L.; Petersen, O. H.

doi:10.1038/339317a0

Cited by 335 publications

(205 citation statements)

References 27 publications

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“…Sensitivity of the inositol 1,4,5-trisphosphate receptor to IP 3 varies widely under different conditions. In vitro studies report sensitivity that varies considerably with the cell type (45)(46)(47), with affinities in the nanomolar range in hepatocytes (48), pancreatic acinar cells (49,50), and smooth muscle (51) but an EC 50 of 25 M in neurons in controlled cytoplasmic environments (52) and intact cell bodies (21,50,53). In experiments on non-neuronal cells, up to 10 M single-caged IP 3 has been used, a concentration that does not activate or block calcium release (12).…”

Section: Discussionmentioning

confidence: 99%

Synapse Specificity of Calcium Release Probed by Chemical Two-photon Uncaging of Inositol 1,4,5-Trisphosphate

Sarkisov

Gelber

Walker

et al. 2007

Journal of Biological Chemistry

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Biological messengers can be "caged" by adding a single photosensitive group that can be photolyzed by a light flash to achieve spatially and temporally precise biochemical control. Here we report that photolysis of a double-caged form of the second messenger inositol 1,4,5-trisphosphate (IP 3 ) triggers focal calcium release in Purkinje cell somata, dendrites, and spines as measured by two-photon microscopy. In calbindin knock-out Purkinje cells, peak calcium increased with flash energy with higher cooperativity for double-caged IP 3 than for conventional single-caged IP 3 , consistent with a chemical twophoton effect. Spine photolysis of double-caged IP 3 led to local calcium release. Uncaging of glycerophosphoryl-myo-inositol 4,5-bisphosphate (gPIP 2 ), a poorly metabolizable IP 3 analog, led to less well localized release. Thus, IP 3 breakdown is necessary for spine-specificity. IP 3 -and gPIP 2 -evoked signals declined from peak with similar, slow time courses, indicating that release lasts hundreds of milliseconds and is terminated not by IP 3 degradation but by intrinsic receptor dynamics. Based on measurements of spine-dendrite coupling, IP 3 -evoked calcium signals are expected to be at least 2.4-fold larger in their spine of origin than in nearby spines, allowing IP 3 to act as a synapsespecific second messenger. Unexpectedly, single-caged IP 3 led to less release in somata and was ineffective in dendrites and spines. Calcium release using caged gPIP 2 was inhibited by the addition of single-caged IP 3 , suggesting that single-caged IP 3 is an antagonist of calcium release. Caging at multiple sites may be an effective general approach to reducing residual receptor interaction.Inositol 1,4,5-trisphosphate binds to receptors on internal organelles, triggering calcium (Ca 2ϩ ) release from stores and thus elevating cytoplasmic calcium concentration. Calcium elevation can trigger a wide variety of physiological responses in many cell types (1). In neurons, inositol 1,4,5-trisphosphate (IP 3 )-triggered calcium release can be extremely rapid, beginning considerably less than 100 ms after synaptic activity (2-4). Such a rapid response implies that IP 3 2 is produced within 10s of ms of receptor activation. Furthermore, calcium release mechanisms nearly always have strong inactivation mechanisms that can depend on recent activation. Therefore, the rapid kinetics of IP 3 concentration and receptor dynamics are key determinants of the properties of calcium release.The properties of IP 3 -dependent calcium release may guide the properties of synaptic plasticity. In cerebellar Purkinje cells, which strongly express IP 3 receptors, IP 3 receptor-mediated calcium release is necessary for the induction of long-term depression of parallel fiber synapses (5, 6). Calcium release in dendritic spines is thought to act as a coincidence detector between parallel fiber activity, which generates IP 3 , and climbing fiber activity, which causes calcium entry that boosts release by acting on the IP 3 receptor (4, 7). In this m...

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Section: Discussionmentioning

confidence: 99%

Synapse Specificity of Calcium Release Probed by Chemical Two-photon Uncaging of Inositol 1,4,5-Trisphosphate

Sarkisov

Gelber

Walker

et al. 2007

Journal of Biological Chemistry

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“…High amplitude, aberrant, intracellular Ca 2ϩ waves that propagate from the apical to basolateral region of the acinar cell predispose to early features of pancreatitis, particularly intra-acinar protease activation (8,9). We know that intracellular Ca 2ϩ release is responsible for the onset of this aberrant Ca 2ϩ signal (10). In addition, we have previously shown that the ryanodine receptor (RYR), 4 a major intracellular Ca 2ϩ channel, is localized to the basolateral region of the acinar cell and, more importantly, is linked to the onset of pathologic protease activation (8).…”

Section: From the Yale University School Of Medicine New Haven Connmentioning

confidence: 99%

Ethanol Enhances Carbachol-induced Protease Activation and Accelerates Ca2+ Waves in Isolated Rat Pancreatic Acini

Orabi¹,

Shah²,

Muili

et al. 2011

Journal of Biological Chemistry

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Alcohol abuse is a leading cause of pancreatitis, accounting for 30% of acute cases and 70 -90% of chronic cases, yet the mechanisms leading to alcohol-associated pancreatic injury are unclear. An early and critical feature of pancreatitis is the aberrant signaling of Ca 2؉ within the pancreatic acinar cell. An important conductor of this Ca 2؉ is the basolaterally localized, intracellular Ca 2؉ channel ryanodine receptor (RYR). In this study, we examined the effect of ethanol on mediating both pathologic intra-acinar protease activation, a precursor to pancreatitis, as well as RYR Ca 2؉ signals. We hypothesized that ethanol sensitizes the acinar cell to protease activation by modulating RYR Ca 2؉ . Acinar cells were freshly isolated from rat, pretreated with ethanol, and stimulated with the muscarinic agonist carbachol (1 M). Ethanol caused a doubling in the carbachol-induced activation of the proteases trypsin and chymotrypsin (p < 0.02). The RYR inhibitor dantrolene abrogated the enhancement of trypsin and chymotrypsin activity by ethanol (p < 0.005 for both proteases). Further, ethanol accelerated the speed of the apical to basolateral Ca 2؉ wave from 9 to 18 m/s (p < 0.0005; n ‫؍‬ 18 -22 cells/group); an increase in Ca 2؉ wave speed was also observed with a change from physiologic concentrations of carbachol (1 M) to a supraphysiologic concentration (1 mM) that leads to protease activation. Dantrolene abrogated the ethanol-induced acceleration of wave speed (p < 0.05; n ‫؍‬ 10 -16 cells/group). Our results suggest that the enhancement of pathologic protease activation by ethanol is dependent on the RYR and that a novel mechanism for this enhancement may involve RYR-mediated acceleration of Ca 2؉ waves.Pancreatitis is a life-threatening inflammatory disorder of the pancreas that leads to more than 30,000 deaths per year (1). Alcohol-associated pancreatitis accounts for 30% of acute cases and 70 -90% of chronic cases. Further, alcoholic pancreatitis carries the highest mortality rate among all etiologies (2). However, the mechanisms by which ethanol mediates pathology are largely unknown.Alcohol can exert diverse effects on the pancreas. Ethanol exposure has been linked to abnormal blood flow, leading to ischemic changes, and increased sphincter of Oddi dysfunction, resulting in pancreatic duct hypertension (2).In addition, ethanol appears to directly predispose the acinar cell to pathological changes including oxidant stress (3), membrane fragility (4), mitochondrial uncoupling (5, 6), and basolateral exocytosis (7). Several lines of evidence also link ethanol to aberrant Ca 2ϩ 3 signaling (6). High amplitude, aberrant, intracellular Ca 2ϩ waves that propagate from the apical to basolateral region of the acinar cell predispose to early features of pancreatitis, particularly intra-acinar protease activation (8, 9). We know that intracellular Ca 2ϩ release is responsible for the onset of this aberrant Ca 2ϩ signal (10). In addition, we have previously shown that the ryanodine receptor (RYR), 4 a major intracel...

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“…In both steady-state and luminal potential models, continuous activation of InsP 3 receptor channels by a constant concentration of InsP 3 [36] and/or openings of other 'leak' channels [37,38] are required for self-sustained oscillation. It may also be argued that such constant openings of Ca 2+ releasing channels are not enough for optimal Ca 2+ release.…”

Section: Ca 2+ Oscillation By 'Quantal' Ca 2+ Releasementioning

confidence: 99%

‘Quantal’ Ca²⁺ release reassessed – a clue to oscillation and synchronization

Yamashita

2006

FEBS Letters

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Ca 2+ release from intracellular Ca 2+ stores, a pivotal event in Ca 2+ signaling, is a 'quantal' process; it terminates after a rapid release of a fraction of stored Ca 2+ . To explain the 'quantal' nature, 'all-or-none' model and 'steady-state' model were proposed. This article shortly reviews these hypotheses and considers a recently proposed mechanism, 'luminal potential ' model, in The release of Ca 2+ from intracellular Ca 2+ stores shows complex kinetic behavior. By examining the kinetics of hormone-mediated 45 Ca 2+ efflux from pre-loaded stores, Muallem et al. [1] found that the Ca 2+ release is a 'quantal' rather than a continuous process; it consists of a rapid release of a fraction of stored Ca 2+ followed by no or a much slower efflux of Ca 2+ . This transient and partial release behavior has been termed 'quantal' Ca 2+ release [1].The 'quantal' release of Ca 2+ requires a mechanism for the attenuation of Ca 2+ efflux, such as inactivation of inositol 1,4,5-trisphosphate (InsP 3 ) receptor channels [2]. However, many studies have provided evidence for the lack of inactivation or desensitization of InsP 3 receptor channels [3][4][5][6][7][8][9]. Alternatively, the efflux of Ca 2+ may be compensated for by reuptake of Ca 2+ after a rapid release of Ca 2+ , as the activity of store Ca 2+ pumps is accelerated by a decrease in the concentration of Ca 2+ in the lumen of the Ca 2+ store [10]. However, this explanation was also unlikely because the transient Ca 2+ release occurs in the absence of Ca 2+ reuptake [3,4,8,9,[11][12][13].Another feature of 'quantal' Ca 2+ release is that the amount of Ca 2+ released depends on the dose of agonist or InsP 3 [1,3,4,6,8,9], or caffeine for ryanodine-sensitive Ca 2+ stores [14,15]. Meyer and Stryer [3] suggested that such dose dependent Ca 2+ release acts as an 'increment detector' in response to stepwise increases in stimulus intensity. To explain the kinetics and the dose dependence of 'quantal' Ca 2+ release, the following two hypotheses were proposed. 'All-or-none' model versus 'steady-state' modelMuallem et al.[1] first postulated that Ca 2+ ions are released from Ca 2+ stores in an all-or-none fashion ('all-or-none' model). Then Irvine [16] proposed another model, in which the sensitivity of InsP 3 receptor to InsP 3 is regulated by the luminal Ca 2+ concentration ('steady-state' model). Since these two models were proposed, numerous studies attempted to support or deny either of the two hypotheses. Missiaen et al.[17] and Bootman [18] extensively reviewed and discussed these hypotheses. The following is a short review of the two models including recent studies. All-or-none modelMuallem et al.[1] have supposed that intracellular Ca 2+ stores are compartmentalized and a submaximal dose of agonist or InsP 3 discharges all the Ca 2+ content in a fraction of the compartmentalized Ca 2+ stores. It is also assumed that the compartments of Ca 2+ store differ in the sensitivity to InsP 3 . According to this model, all the stored Ca 2+ ions are released fro...

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Pulsatile intracellular calcium release does not depend on fluctuations in inositol trisphosphate concentration

Cited by 335 publications

References 27 publications

Synapse Specificity of Calcium Release Probed by Chemical Two-photon Uncaging of Inositol 1,4,5-Trisphosphate

Synapse Specificity of Calcium Release Probed by Chemical Two-photon Uncaging of Inositol 1,4,5-Trisphosphate

Ethanol Enhances Carbachol-induced Protease Activation and Accelerates Ca2+ Waves in Isolated Rat Pancreatic Acini

‘Quantal’ Ca²⁺ release reassessed – a clue to oscillation and synchronization

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Pulsatile intracellular calcium release does not depend on fluctuations in inositol trisphosphate concentration

Cited by 335 publications

References 27 publications

Synapse Specificity of Calcium Release Probed by Chemical Two-photon Uncaging of Inositol 1,4,5-Trisphosphate

Synapse Specificity of Calcium Release Probed by Chemical Two-photon Uncaging of Inositol 1,4,5-Trisphosphate

Ethanol Enhances Carbachol-induced Protease Activation and Accelerates Ca2+ Waves in Isolated Rat Pancreatic Acini

‘Quantal’ Ca2+ release reassessed – a clue to oscillation and synchronization

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‘Quantal’ Ca²⁺ release reassessed – a clue to oscillation and synchronization