A Statistical View on Calcium Oscillations

Powell, Jake; Falcke, Martin; Skupin, Alexander; Bellamy, Tomas C.; Kypraios, Theodore; Thul, Ruediger

doi:10.1007/978-3-030-12457-1_32

Cited by 14 publications

(7 citation statements)

References 83 publications

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“…Another limitation of the models referred here is that they are based on the “well-stirred-reactor” assumption where all components of the signaling cascade are uniformly distributed in the cytoplasm. A state-of-art approach is to model the system as a reaction-diffusion process using partial differential equations and incorporation of stochastic parameters that are less assumptive and accounts for the inherent variability in receptor states at different time points [ 77 , 78 ]. However, such an approach is computationally expensive.…”

Section: [ Ca C 2+ ]-Sigmentioning

confidence: 99%

GPCR mediated control of calcium dynamics: A systems perspective

Dhyani

Gare

Gupta

et al. 2020

Cellular Signalling

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G-protein coupled receptor (GPCR) mediated calcium (Ca 2+)-signaling transduction remains crucial in designing drugs for various complex diseases including neurodegeneration, chronic heart failure as well as respiratory diseases. Although there are several reviews detailing various aspects of Ca 2+-signaling such as the role of IP 3 receptors and Ca 2+-induced-Ca 2+-release, none of them provide an integrated view of the mathematical descriptions of GPCR signal transduction and investigations on dose-response curves. This article is the first study in reviewing the network structures underlying GPCR signal transduction that control downstream [Ca c 2+ ]oscillations. The central theme of this paper is to present the biochemical pathways, as well as molecular mechanisms underlying the GPCR-mediated Ca 2+-dynamics in order to facilitate a better understanding of how agonist concentration is encoded in Ca 2+-signals for G αq , G αs , and G αi/o signaling pathways. Moreover, we present the GPCR targeting drugs that are relevant for treating cardiac, respiratory, and neuro-diseases. The current paper presents the ODE formulation for various models along with the detailed schematics of signaling networks. To provide a systems perspective, we present the network motifs that can provide readers an insight into the complex and intriguing science of agonist-mediated Ca 2+-dynamics. One of the features of this review is to pinpoint the interplay between positive and negative feedback loops that are involved in controlling intracellular [Ca c 2+ ]-oscillations. Furthermore, we review several examples of dose-response curves obtained from [Ca c 2+ ]-spiking for various GPCR pathways. This paper is expected to be useful for pharmacologists and computational biologists for designing clinical applications of GPCR targeting drugs through modulation of Ca 2+dynamics.

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Section: [ Ca C 2+ ]-Sigmentioning

confidence: 99%

GPCR mediated control of calcium dynamics: A systems perspective

Dhyani

Gare

Gupta

et al. 2020

Cellular Signalling

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“…Although Ca 2+ oscillations are intrinsically stochastic because of stochastic IP 3 R channel dynamics (Powell et al, 2020;Thul, 2014;Thurley et al, 2012), the Ca 2+ oscillations at the cellular level can be effectively treated as deterministic (Cao et al, 2014;Sneyd et al, 2017;Voorsluijs et al, 2019). As a result, we only used the two-variable Li-Rinzel model as the simplest but useful model to produce Ca 2+ oscillations.…”

Section: Limitations Of the Studymentioning

confidence: 99%

The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction

Jin

et al. 2020

iScience

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Although a rising concentration of cytosolic Ca 2+ has long been recognized as an essential signal for apoptosis, the dynamical mechanisms by which Ca 2+ regulates apoptosis are not clear yet. To address this, we constructed a computational model that integrates known biochemical reactions and can reproduce the dynamical behaviors of Ca 2+ -induced apoptosis as observed in experiments. Model analysis shows that oscillating Ca 2+ signals first convert into gradual signals and eventually transform into a switch-like apoptotic response. Via the two processes, the apoptotic signaling pathway filters the frequency of Ca 2+ oscillations effectively but instead responds acutely to their amplitude. Collectively, our results suggest that Ca 2+ regulates apoptosis mainly via oscillation amplitude, rather than frequency, modulation. This study not only provides a comprehensive understanding of how oscillatory Ca 2+ dynamically regulates the complex apoptotic signaling network but also presents a typical example of how Ca 2+ controls cellular responses through amplitude modulation.

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“…Both approaches have been used extensively to date as e.g. in (Dupont et al, 2011b;Falcke et al, 2018;Gaspers et al, 2014;Kummer et al, 2000;Li and Rinzel, 1994a;Politi et al, 2006;Powell et al, 2020;Shuai and Jung, 2002;Skupin et al, 2008;Sneyd et al, 2017;Sun et al, 2017;Tang et al, 1996;Thul et al, 2009;Thul and Falcke, 2007, 2004aThurley et al, 2011;Tilunaite et al, 2017;Thul, 2014;Thurley et al, 2012;Tsaneva-Atanasova et al, 2005;Voorsluijs et al, 2019;Weinberg and Smith, 2014;Wieder et al, 2015) -see also the book by (Dupont et al, 2016b) for a detailed discussion. As this study is the first to explore the role of Ca 2+ in a mathematical model of cancer cell propagation, we opted for a deterministic approach.…”

Section: Summary Conclusion and Further Workmentioning

confidence: 99%

Adhesion-driven patterns in a calcium-dependent model of cancer cell movement

Kaouri¹,

Bitsouni²,

Buttenschön³

et al. 2020

Preprint

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Cancer cells exhibit increased motility and proliferation, which are instrumental in the formation of tumours and metastases. These pathological changes can be traced back to malfunctions of cellular signalling pathways, and calcium signalling plays a prominent role in these. We formulate a new model for cancer cell movement which for the first time explicitly accounts for the dependence of cell proliferation and cell-cell adhesion on calcium. At the heart of our work is a non-linear, integro-differential (non-local) equation for cancer cell movement, accounting for cell diffusion, advection and proliferation. We also employ an established model of cellular calcium signalling with a rich dynamical repertoire that includes experimentally observed periodic wave trains and solitary pulses. The cancer cell density exhibits travelling fronts and complex spatial patterns arising from an adhesion-driven instability (ADI). We show how the different calcium signals and variations in the strengths of cell-cell attraction and repulsion shape the emergent cellular aggregation patterns, which are a key component of the metastatic process. Performing a linear stability analysis, we identify parameter regions corresponding to ADI. These regions are confirmed by numerical simulations, which also reveal different types of aggregation patterns and these patterns are significantly affected by Ca 2+ . Our study demonstrates that the maximal cell density decreases with calcium concentration, while the frequencies of the calcium oscillations and the cell density oscillations are approximately equal in many cases. Furthermore, as the calcium levels increase the speed of the travelling fronts increases, which is related to a higher cancer invasion potential. These novel insights provide a step forward in the design of new cancer treatments that may rely on controlling the dynamics of cellular calcium.

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A Statistical View on Calcium Oscillations

Cited by 14 publications

References 83 publications

GPCR mediated control of calcium dynamics: A systems perspective

GPCR mediated control of calcium dynamics: A systems perspective

The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction

Adhesion-driven patterns in a calcium-dependent model of cancer cell movement

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