Establishing the stochastic nature of intracellular calcium oscillations from experimental data

Rapid non-genomic effects of 17␤-estradiol, the principal circulating estrogen, have been observed in a wide variety of cell types. Here we investigate rapid signaling effects of 17␤-estradiol in rat hepatocytes. We show that, above a threshold concentration of 1 nM, 17␤-estradiol, but not 17␣-estradiol, stimulates particulate guanylyl cyclase to elevate cGMP, which through activation and plasma membrane recruitment of protein kinase G isoform I␣, stimulates plasma membrane Ca 2؉ -ATPase-mediated Ca 2؉ efflux from rat hepatocytes. These effects are extremely rapid in onset and are mimicked by a membrane-impermeant 17␤-estradiol-BSA conjugate, suggesting that 17␤-estradiol acts at the extracellular face of the plasma membrane. We also show that 17␤-estradiol binds specifically to the intact hepatocyte plasma membrane through an interaction that is competed by an excess of atrial natriuretic peptide but also shows many similarities to the pharmacological characteristics of the putative ␥-adrenergic receptor. We, therefore, propose that the observed rapid signaling effects of 17␤-estradiol are mediated either through the guanylyl cyclase A receptor for atrial natriuretic peptide or through the ␥-adrenergic receptor, which is either itself a transmembrane guanylyl cyclase or activates a transmembrane guanylyl cyclase through cross-talk signaling.

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“…Single hepatocytes were isolated from 150 -250 g of female Wistar rats by collagenase digestion as described previously (62,63).…”

Section: Isolation Of Hepatocytesmentioning

confidence: 99%

17β-Estradiol Elevates cGMP and, via Plasma Membrane Recruitment of Protein Kinase GIα, Stimulates Ca2+ Efflux from Rat Hepatocytes

Stratton

Squires

Green

2010

Journal of Biological Chemistry

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“…Mathematically, a linear system of inequalities and equations can be solved by the Simplex method even when containing many unknowns. By this method we find a set of solutions to (8) and (9). It is…”

Section: Applicationsmentioning

confidence: 99%

A Positive Real Eigenvalue Condition for the Determination of Unstable Steady States in Chemical Reaction Networks

Chao

Chuang

et al. 2008

Zeitschrift Für Naturforschung A

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The interesting dynamical behaviours exhibiting in chemical reaction systems, such as multiple steady states and undamped oscillations, often result from unstable steady states. A positive real eigenvalue condition is proposed which gives a necessary and sufficient condition for the determination of an unstable steady state having a positive real eigenvalue in general isothermal reaction networks. Formulas are developed to construct an unstable steady state and a set of positive rate constants. The applications are illustrated by three examples. Two give rise to oscillations and one admits multiple steady states.

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“…Transfer of IP 3 across gap-junctions (connexins) may also contribute for the calcium elevation [4], though in a minor degree [2,5,6]. Other recent studies have shown that intracellular Ca 2+ oscillations are basically a form of correlated noise [7], which raises the question of stochasticity and reproducibility of the signal propagation and the corresponding network. While questions concerning the details of the propagating mechanisms remain an important matter of discussion [8], we are here interested in extracting insight from the inter-connectivity between cells by keeping track of Ca 2+ signals.…”

Section: Introductionmentioning

confidence: 99%

Modeling the functional network of primary intercellular Ca2+ wave propagation in astrocytes and its application to study drug effects

Pires

Raischel

Vaz

et al. 2014

Journal of Theoretical Biology

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We introduce a simple procedure of multivariate signal analysis to uncover the functional connectivity among cells composing a living tissue and describe how to apply it for extracting insight on the effect of drugs in the tissue. The procedure is based on the covariance matrix of time resolved activity signals. By determining the time-lag that maximizes covariance, one derives the weight of the corresponding connection between cells. Introducing simple constraints, it is possible to conclude whether pairs of cells are functionally connected and in which direction. After testing the method against synthetic data we apply it to study intercellular propagation of Ca 2+ waves in astrocytes following an external stimulus, with the aim of uncovering the functional cellular connectivity network. Our method proves to be particularly suited for this type of networking signal propagation where signals are pulse-like and have short time-delays, and is shown to be superior to standard methods, namely a multivariate Granger algorithm. Finally, based the statistical analysis of the connection weight distribution, we propose simple measures for assessing the impact of drugs on the functional connectivity between cells.

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Establishing the stochastic nature of intracellular calcium oscillations from experimental data

Cited by 88 publications

References 55 publications

17β-Estradiol Elevates cGMP and, via Plasma Membrane Recruitment of Protein Kinase GIα, Stimulates Ca2+ Efflux from Rat Hepatocytes

17β-Estradiol Elevates cGMP and, via Plasma Membrane Recruitment of Protein Kinase GIα, Stimulates Ca2+ Efflux from Rat Hepatocytes

A Positive Real Eigenvalue Condition for the Determination of Unstable Steady States in Chemical Reaction Networks

Modeling the functional network of primary intercellular Ca2+ wave propagation in astrocytes and its application to study drug effects

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