IP3-Dependent Ca2+ Oscillations Switch into a Dual Oscillator Mechanism in the Presence of PLC-Linked Hormones

  title={IP3-Dependent Ca2+ Oscillations Switch into a Dual Oscillator Mechanism in the Presence of PLC-Linked Hormones},
  author={Paula J. Bartlett and Ielyaas Cloete and James Sneyd and Andrew P Thomas},
Summary Ca2+ oscillations that depend on inositol-1,4,5-trisphosphate (IP3) have been ascribed to biphasic Ca2+ regulation of the IP3 receptor (IP3R) or feedback mechanisms controlling IP3 levels in different cell types. IP3 uncaging in hepatocytes elicits Ca2+ transients that are often localized at the subcellular level and increase in magnitude with stimulus strength. However, this does not reproduce the broad baseline-separated global Ca2+ oscillations elicited by vasopressin. Addition of… Expand
Receptor-specific Ca2+ oscillation patterns mediated by differential regulation of P2Y purinergic receptors in rat hepatocytes
The PKC leg of the bifurcated IP3 signaling pathway shapes unique Ca2+ oscillation patterns that allows for distinct cellular responses to different agonists. Expand
Purinergic P2Y1 and P2Y2/4 receptors elicit distinct Ca2+ signaling patterns in hepatocytes via differential feedback regulation by Protein Kinase C
Extracellular nucleotides are key regulators of liver physiology. In primary rat hepatocytes, P2Y1 receptor (P2Y1R) activation by ADP generates cytosolic calcium ([Ca2+]c) oscillations with narrowExpand
Modeling of Ca2+ transients initiated by GPCR agonists in mesenchymal stromal cells
Abstract The integrative study that included experimentation and mathematical modeling was carried out to analyze dynamic aspects of transient Ca2+ signaling induced by brief pulses of GPCR agonistsExpand
Deregulation of Ca2+-Signaling Systems in White Adipocytes, Manifested as the Loss of Rhythmic Activity, Underlies the Development of Multiple Hormonal Resistance at Obesity and Type 2 Diabetes
It is suggested that universal mechanisms underlie loss of rhythmicity, Ca2+-signaling systems deregulation, and development of general hormonal resistance to obesity. Expand
Ethanol Disrupts Hormone-Induced Calcium Signaling in Liver
It is proposed that by suppressing hormone-stimulated PLC activity, ethanol interferes with the dynamic modulation of [IP3] that is required to generate large, amplitude Ca2+ oscillations. Expand
Overview of Ca2+ signaling in lung cancer progression and metastatic lung cancer with bone metastasis
This review dissects and summarizes the important roles of Ca2+ signaling transduction in contributing to lung cancer progression, and addresses the question: if and how Ca2- signaling might have been engaged in metastatic lung cancer with bone metastasis, thereby potentially providing the multifaceted and promising solutions for therapeutic intervention. Expand


Hormone-Induced Calcium Oscillations Depend on Cross-Coupling with Inositol 1,4,5-Trisphosphate Oscillations
A recombinant IP3 buffer is constructed using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range and perturbed [Ca2+]i oscillations in a dose-dependent manner. Expand
Differential Regulation of Multiple Steps in Inositol 1,4,5-Trisphosphate Signaling by Protein Kinase C Shapes Hormone-stimulated Ca2+ Oscillations*
Comparison of IP3 uncaging and hormone stimulation showed that PKC has distinct effects on IP3 formation, metabolism, IP3 receptor function, and Ca2+ wave propagation, and PKC modulates Ca2- oscillation frequency, duration, and wave velocity. Expand
Models of IP3 and Ca2+ oscillations: frequency encoding and identification of underlying feedbacks.
The ectopic expression of an IP3 binding protein has been used to decrease the rate of IP3 turnover experimentally, resulting in a dose-dependent slowing and eventual quenching of the Ca2+ oscillations, consistent with a model based on positive feedback of Ca2- on IP3 production. Expand
Cytosolic Ca2+ oscillations in REF52 fibroblasts: Ca(2+)-stimulated IP3 production or voltage-dependent Ca2+ channels as key positive feedback elements.
Evidence is presented that such oscillations are linked to fluctuations in the concentration of IP3 and the Ca2+ content of an IP3-sensitive Ca2+, and their mechanisms are compared. Expand
A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration.
  • G. D. De Young, J. Keizer
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1992
A simplified kinetic model is constructed to describe the properties of the Ca2+ activation and inhibition of the inositol 1,4,5-trisphosphate (IP3) receptor in the endoplasmic reticulum and finds that it reproduces a variety of in vivo and in vitro experiments. Expand
Initiation of IP3‐mediated Ca2+ waves in Xenopus oocytes
An optical method is developed for evoking rapid subcellular Ca2+ elevations, while independently photoreleasing IP3 and simultaneously recording confocalCa2+ images, which indicates that delayed wave initiation did not involve slow binding of IP3 to its receptors. Expand
Role of elementary Ca2+ puffs in generating repetitive Ca2+ oscillations
The roles of puffs in determining the periodicity of global Ca2+ waves are investigated using video‐rate confocal imaging and photorelease of IP3 in Xenopus oocytes to identify specific ’focal‘ sites that preferentially entrain both the temporal frequency and spatial directionality of Ca2+. Expand
Calcium signaling in liver.
The characteristics of agonist-evoked [Ca2+]i signals in the liver are described and possible mechanisms to explain the propagation of intercellular Ca2+ waves in the intact organ are discussed. Expand
The Spatial Distribution of Inositol 1,4,5-Trisphosphate Receptor Isoforms Shapes Ca2+ Waves*
Findings provide evidence that the apical concentration of type II InsP3Rs is essential for the formation of Ca2+ waves in hepatocytes and the subcellular distribution of InsP1,4,5-trisphosphate receptor isoforms may critically determine the repertoire of spatial patterns ofCa2+ signals. Expand
A method for determining the dependence of calcium oscillations on inositol trisphosphate oscillations.
It is shown that muscarinic receptor-mediated, long- period Ca2+ oscillations in pancreatic acinar cells depend on [IP3] oscillations, whereas short-period Ca2+, airway smooth muscle do not. Expand