IP3 Dynamics Research Articles

Impact of Interdependent Ca2+ and IP3 Dynamics On ATP Regulation in A Fibroblast Model.

The vital participation of Ca2+ in human organ functions such as muscular contractions, heartbeat, brain functionality, skeletal activity, etc, motivated the scientists to thoroughly research the mechanisms of calcium (Ca2+) signalling in distinct human cells. Ca2+, inositol triphosphate (IP3), and adenosine triphosphate (ATP) play important roles in cell signaling and physiological processes. ATP and its derivatives are hypothesized to be important in the pathogenic process that leads to fibrotic illnesses like fibrosis. Fluctuations in Ca2+ and IP3 in a fibroblast cell influence ATP production. To date, no evidence of coupled Ca2+ and IP3 mechanics regulating ATP generation in a fibroblast cell during fibrotic disease has been found. The current work suggests an integrated mechanism for Ca2+ and IP3 dynamics in a fibroblast cell that regulates ATP generation. Simulation has been carried out using the finite element approach. The mechanics of interdependent systems findings vary dramatically from the results of basic independent system mechanics and give fresh information about the two systems' activities. The numerical results provide new insights into the impacts of disturbances in source influx, the serca pump, and buffers on interdependent Ca2+ and IP3 dynamics and ATP synthesis in a fibroblast cell. According to the findings of this study, fibrotic disorders cannot be attributed solely to disruptions in the processes of calcium signaling mechanics but also to disruptions in IP3 regulation mechanisms affecting the regulation of calcium in the fibroblast cell and ATP release.

Fractional-order reaction–diffusion model to study the dysregulatory impacts of superdiffusion and memory on neuronal calcium and IP3 dynamics

Fractional-order reaction–diffusion model to study the dysregulatory impacts of superdiffusion and memory on neuronal calcium and IP3 dynamics

MODEL TO STUDY INTERDEPENDENT CALCIUM AND IP3 DISTRIBUTION REGULATING NFAT PRODUCTION IN T LYMPHOCYTE

The cooperative system of calcium (Ca[Formula: see text]) and inositol 1,4,5-trisphosphate (IP3) plays a crucial role in maintaining structure and functions of T lymphocyte cells including the production of nuclear factor of activated T cells (NFAT) as an immunological response. NFAT regulates several mechanisms and dysregulation in this process can lead to various disorders like inflammatory bowel diseases, etc. In this study, the two-way feedback model of Ca[Formula: see text] and IP3 dynamics regulating NFAT production in T lymphocytes has been constructed. A system of nonlinear reaction-diffusion equations for calcium and IP3 for a one-dimensional case has been employed in this proposed model. The numerical simulation is performed using finite element and the Crank–Nicholson method. The effects of the parameters like Ryanodine Receptor (RyR), source amplitude and buffers on active NFAT production have been analyzed. The novel insights about regulatory and dysregulation events and mechanisms of Ca[Formula: see text], IP3 and NFAT are concluded from these results.

Effect of disturbances in neuronal calcium and IP3 dynamics on β-amyloid production and degradation.

Overproduction and accumulation of β-amyloid and its improper clearance can cause neurotoxicity leading to Alzheimer's disease. The production and degradation of β-amyloid depend on the calcium ([Ca2+]) and IP3 dynamics in the nerve cells. Thus, there is a need to understand the impacts of disturbances in the processes of [Ca2+] and IP3 dynamics on β-amyloid production and its degradation. Here, a model is proposed to investigate the role of [Ca2+] and IP3 dynamics on β-amyloid production and degradation. The problem is formulated in terms of the initial boundary value problem involving the system of two reaction-diffusion equations respectively for [Ca2+] and IP3 in the nerve cell. The solution is obtained by employing the Finite element approach. The numerical results are used to analyze the impact of various mechanisms of calcium and IP3 dynamics on β-amyloid production and degradation in a neuron cell. The results indicate that disturbances in any of the constitutive processes of interdependent calcium and IP3 dynamics like source influx, buffering, serca pump, and IP3 dynamics, etc. can cause dynamic changes in β-amyloid production and degradation, which in turn can be the cause of neurotoxicity and neuronal disorders like Alzheimer's disease. Thus, the relationships obtained by the proposed model among various mechanisms can be useful in addressing the challenges of identifying specific constitutive processes causing neuronal disorders like Alzheimer's disease, etc., and developing the framework for their diagnosis and treatment.

Effects of disorders in interdependent calcium and IP3 dynamics on nitric oxide production in a neuron cell

Effects of disorders in interdependent calcium and IP3 dynamics on nitric oxide production in a neuron cell

Inositol trisphosphate dynamics underlie physiological calcium signals within the coronary artery endothelium

The arterial endothelium modulates smooth muscle tone in response to its local hemodynamic environment. This process is critical to normal vascular function, and is impaired by endothelial cell injury in coronary artery disease. Last year, we discovered a unique mode of calcium signaling of the porcine coronary artery endothelium, characterized by a pattern of continuous, cell‐wide calcium waves in the absence of agonist stimulation. Stimulation with substance P (10−13 to 10−6 ml/L) amplified this pattern to match dose‐dependent vessel relaxation responses. Here, we investigated the mechanism underlying the formation of this characteristic pattern of endothelial calcium waves with confocal microscopy, utilizing both pharmacological and computational approaches. We found that coronary endothelial cell calcium waves were mediated by inositol trisphosphate receptors (IP3R), which exhibited distinct intracellular isoform distributions. The distribution of the type 1 IP3R isoform corresponded to the area (33.9 ± 2.6 μm2) of propagating calcium waves, including perinuclear IP3R clustering at subcellular sites of constitutively elevated calcium. We utilized a computational model of calcium signaling that included this distinct IP3R distribution, and discovered that cell‐wide waves formed only if intracellular concentration gradients of inositol trisphosphate (IP3) were present along the longitudinal cell axis. Importantly, we found that production and diffusion of IP3 from a focal intracellular source was sufficient to initiate a calcium wave event with the same propagation velocity curve (mean: 6.08 ± 0.61 μm/s) of the experimentally‐observed wave. Furthermore, amplification of IP3 production in our model resulted in an increase of the frequency of elementary wave events which reflected the dose‐dependent expansion of calcium activity induced by substance P. These results indicate a fundamental role for IP3 dynamics as a physiological mediator of vascular responses, underlying both the initiation and expansion of unique endothelial calcium signal modalities.Support or Funding InformationThis work was supported by NIH grants: HL136869, HL085887, and S10RR027535.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Multi-Scale Impact of the Alzheimer’s Disease on the Topology Diversity of Astrocytes Molecular Communications Nanonetworks

The Internet of Bio-Nano-Things is a new paradigm that can bring novel remotely controlled actuation and sensing techniques inside the human body. Toward precise bionano sensing techniques in the brain, we investigate the challenges of modeling spatial distribution of astrocyte networks by developing a mathematical framework that lays the groundwork for future early detection techniques of the neurodegenerative disease. In this paper, we investigate the effect of the $\beta $ -amyloid plaques in astrocytes with Alzheimer’s disease. We developed a computation model of healthy and Alzheimer’s diseases astrocytes networks from the state-of-the-art models and results that account for the intracellular pathways, IP3 dynamics, gap junctions, voltage-gated calcium channels, and astrocytes volumes. We also implemented different types of astrocytes network topologies, including shortcut networks, regular degree networks, Erdos Renyi networks, and link radius networks. A proposed multi-scale stochastic computational model captures the relationship between the intracellular and intercellular scales. Finally, we designed and evaluated a single-hop communication system with frequency modulation using metrics such as propagation extend, molecular delay, and channel gain. The results show that the more unstable but at the same time lower level oscillations of Alzheimer’s astrocyte networks can create a multi-scale effect on communication between astrocytes with increased molecular delay and lower channel gain compared to healthy astrocytes, with an elevated impact on Erdos Renyi network and link radius network topologies.

Advances in methods for analyzing IP3 signaling and understanding of coupled Ca2+ and IP3 oscillations

Inositol 1,4,5-trisphosphate (IP3) is an important intracellular messenger produced by phospholipase C via the activation of G-protein-coupled receptor- or receptor-tyrosine-kinase-mediated pathways, and is involved in numerous responses to hormones, neurotransmitters, and growth factors through the releases of Ca2+ from intracellular stores via IP3 receptors. IP3-mediated Ca2+ signals often exhibit complex spatial and temporal organizations, such as Ca2+ oscillations. Recently, new methods have become available to measure IP3 concentration ([IP3]) using AlphaScreen technology, fluorescence polarization, and competitive ligand binding assay (CFLA). These methods are useful for the high throughput screening in drug discovery. Calcium ions generate versatile intracellular signals such as Ca2+ oscillations and waves. Fluorescent sensors molecules to monitor changes in [IP3] in single living cells are crucial to study the mechanism for the spatially and temporally regulated Ca2+ signals. In particular, FRET-based IP3 sensors are useful for the quantitative monitoring intracellular [IP3], and allowed to uncovered the oscillatory IP3 dynamics in association with Ca2+ oscillations. A mathematical model of coupled Ca2+ and IP3 oscillations predicts that Ca2+ oscillations are the result of modulation of the IP3 receptor by intracellular Ca2+, and that the period is modulated by the accompanying IP3 oscillations. These model predictions have also been confirmed experimentally. At present, however, usefulness of FRET-based IP3 sensors are limited by their relatively small change in fluorescence. Development of novel IP3 sensors with improve dynamic range would be important for understanding the regulatory mechanism of Ca2+ signaling and for in vivo IP3 imaging.

Hormone-Induced Calcium Oscillations Depend on Cross-Coupling with Inositol 1,4,5-Trisphosphate Oscillations

SUMMARYReceptor-mediated oscillations in cytosolic Ca2+ concentration ([Ca2+]i) could originate either directly from an autonomous Ca2+ feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca2+ feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca2+ oscillations or could just be a secondary response to the [Ca2+]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range. This IP3 buffer slows hormone-induced [IP3] dynamics without changing steady-state [IP3]. GFP-LBD perturbed [Ca2+]i oscillations in a dose-dependent manner: it decreased both the rate of [Ca2+]i rise and the speed of Ca2+ wave propagation and, at high levels, abolished [Ca2+]i oscillations completely. These data, together with computational modeling, demonstrate that IP3 dynamics play a fundamental role in generating [Ca2+]i oscillations and waves.

Calcium and IP3 dynamics in cardiac myocytes: experimental and computational perspectives and approaches

Calcium plays a crucial role in excitation-contraction coupling (ECC), but it is also a pivotal second messenger activating Ca2+-dependent transcription factors in a process termed excitation-transcription coupling (ETC). Evidence accumulated over the past decade indicates a pivotal role of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release in the regulation of cytosolic and nuclear Ca2+ signals. IP3 is generated by stimulation of plasma membrane receptors that couple to phospholipase C (PLC), liberating IP3 from phosphatidylinositol 4,5-bisphosphate (PIP2). An intriguing aspect of IP3 signaling is the presence of the entire PIP2-PLC-IP3 signaling cascade as well as the presence of IP3Rs at the inner and outer membranes of the nuclear envelope (NE) which functions as a Ca2+ store. The observation that the nucleus is surrounded by its own putative Ca2+ store raises the possibility that nuclear IP3-dependent Ca2+ release plays a critical role in ETC. This provides a potential mechanism of regulation that acts locally and autonomously from the global cytosolic Ca2+ signal underlying ECC. Moreover, there is evidence that: (i) the sarcoplasmic reticulum (SR) and NE are a single contiguous Ca2+ store; (ii) the nuclear pore complex is the major gateway for Ca2+ and macromolecules to pass between the cytosol and the nucleoplasm; (iii) the inner membrane of the NE hosts key Ca2+ handling proteins including the Na+/Ca2+ exchanger (NCX)/GM1 complex, ryanodine receptors (RyRs), nicotinic acid adenine dinucleotide phosphate receptors (NAADPRs), Na+/K+ ATPase, and Na+/H+ exchanger. Thus, it appears that the nucleus represents a Ca2+ signaling domain equipped with its own ion channels and transporters that allow for complex local Ca2+ signals. Many experimental and modeling approaches have been used for the study of intracellular Ca2+ signaling but the key to the understanding of the dual role of Ca2+ mediating ECC and ECT lays in quantitative differences of local [Ca2+] in the nuclear and cytosolic compartment. In this review, we discuss the state of knowledge regarding the origin and the physiological implications of nuclear Ca2+ transients in different cardiac cell types (adult atrial and ventricular myocytes) as well as experimental and mathematical approaches to study Ca2+ and IP3 signaling in the cytosol and nucleus. In particular, we focus on the concept that highly localized Ca2+ signals are required to translocate and activate Ca2+-dependent transcription factors (e.g., nuclear factor of activated T-cells, NFAT; histone deacetylase, HDAC) through phosphorylation/dephosphorylation processes.

Phospholipase C-β1 and β4 Contribute to Non-Genetic Cell-to-Cell Variability in Histamine-Induced Calcium Signals in HeLa Cells

A uniform extracellular stimulus triggers cell-specific patterns of Ca2+ signals, even in genetically identical cell populations. However, the underlying mechanism that generates the cell-to-cell variability remains unknown. We monitored cytosolic inositol 1,4,5-trisphosphate (IP3) concentration changes using a fluorescent IP3 sensor in single HeLa cells showing different patterns of histamine-induced Ca2+ oscillations in terms of the time constant of Ca2+ spike amplitude decay and the Ca2+ oscillation frequency. HeLa cells stimulated with histamine exhibited a considerable variation in the temporal pattern of Ca2+ signals and we found that there were cell-specific IP3 dynamics depending on the patterns of Ca2+ signals. RT-PCR and western blot analyses showed that phospholipase C (PLC)-β1, -β3, -β4, -γ1, -δ3 and -ε were expressed at relatively high levels in HeLa cells. Small interfering RNA-mediated silencing of PLC isozymes revealed that PLC-β1 and PLC-β4 were specifically involved in the histamine-induced IP3 increases in HeLa cells. Modulation of IP3 dynamics by knockdown or overexpression of the isozymes PLC-β1 and PLC-β4 resulted in specific changes in the characteristics of Ca2+ oscillations, such as the time constant of the temporal changes in the Ca2+ spike amplitude and the Ca2+ oscillation frequency, within the range of the cell-to-cell variability found in wild-type cell populations. These findings indicate that the heterogeneity in the process of IP3 production, rather than IP3-induced Ca2+ release, can cause cell-to-cell variability in the patterns of Ca2+ signals and that PLC-β1 and PLC-β4 contribute to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation.

The Relationship Between Ip 3 Level and the Frequency of Ca 2+ Oscillations

Many cellular stimuli induce oscillations of cytosolic calcium concentration ([Ca2+]). Ca2+ signals are generated by a cascade involving agonist binding to G protein-coupled receptor (GPCR), generation of inositol 1,4,5-trisphosphate (IP3), release of Ca2+ from endoplasmic reticulum through IP3 receptor (IP3R).In the previous study, we have developed Forster resonance energy transfer based IP3 sensors and monitored the IP3 dynamics during Ca2+ oscillations. In stimulated HeLa cells, IP3 started to increase at a relatively constant rate before the pacemaker Ca2+ rise, and IP3 gradually accumulated in the cytosol with a little fluctuations during cytosolic Ca2+ oscillations. In this study, we compared the relationship between IP3 concentration ([IP3]) and the frequency of Ca2+ oscillations, and found they are well correlated but the relationships are different among the types of stimulated GPCRs. This result shows the frequency of Ca2+ oscillations are not only determined by [IP3]. To explain the result, we developed a kinetic model that reproduces Ca2+ and IP3 dynamics observed in HeLa cells by constructing a novel 6-state IP3R model. We found that Ca2+-dependent regulation of IP3-binding affinity of IP3R and the feedback regulation of phospholipase C, which produces IP3 from phosphatidylinositol 4,5-bisphosphate, by cytosolic Ca2+ are essential ingredients in the model.

The Development of FRET-Based IP3 Biosensors and Their Use for Monitoring IP3 Dynamics during Ca2+ Oscillations and Ca2+ Waves in Non-Excitable Cells

The Development of FRET-Based IP3 Biosensors and Their Use for Monitoring IP3 Dynamics during Ca2+ Oscillations and Ca2+ Waves in Non-Excitable Cells

Mechanism of Calcium Waves and Oscillations in Non-Excitable Cells

The functions of salivary acinar cells are regulated by the activation of receptors on their basolateral membranes and by subsequent intracellular signaling events, including increases in cytoplasmic Ca2+ ([Ca2+]i) and cyclic AMP (cAMP) production. Ca2+ plays essential roles in fluid and electrolyte secretions from salivary acinar cells. A typical agonist-induced Ca2+ response in salivary acinar cells shows Ca2+ waves, in which the rise in [Ca2+]i is initiated at the apical pole before spreading towards the basal region of the cell. Ca2+ responses with low concentrations of agonist often occur result in repetitive transient rises in [Ca2+]i, which have been referred to as Ca2+ oscillations. These spatial characteristics of the Ca2+ signal are primarily determined by the distribution of the endoplasmic reticulum (ER) and inositol 1,4,5-trisphosphate (IP3) receptors, which correspond to the major intracellular Ca2+ store and Ca2+ releasing channels, respectively. ER cisternae are densely packed in the entire basolateral region, whereas small ER vesicular structures are located in the apical region of acinar cells. This apparent paradox would be resolved if it could be shown that the small Ca2+-releasing ER elements in the apical region are connected to the main part of the ER in the basolateral area. Although the mitochondria are not considered to be a physiological Ca2+ store, accumulating evidence indicates that mitochondria play a significant role in the regulation of the spatial and temporal patterns of Ca2+ signals. The mechanism that is responsible for Ca2+ oscillations remain controversial. Two general models for Ca2+ oscillations have been proposed ; one explains Ca2+ oscillations generated by constant cytoplasmic IP3 concentrations [IP3]i) and the other explains Ca2+ oscillations generated by oscillating [IP3]i. Quantitative measurements of [IP3]i using fluorescent IP3 biosensors revealed two cell type-specific differences in IP3 dynamics : non-fluctuating rises in [IP3]i and repetitive IP3 spikes during Ca2+ oscillations. However, the repetitive IP3 spikes are thought to be passive reflections of Ca2+ oscillations, and are unlikely to be essential for driving Ca2+ oscillations. Regarding the mechanism of Ca2+ oscillations, the importance of dual feedback effects of Ca2+ on IP3Rs has been demonstrated experimentally, while the precise mechanism responsible for establishing these oscillations remains unclear. In addition to the necessity of continuing work on the mechanisms that control Ca2+ oscillations, an important challenge for the future will be to determine how these patterns of Ca2+ signaling systems function in specific cellular processes.

Monitoring of IP3 dynamics during Ca2+ oscillations in HSY human parotid cell line with FRET-based IP3 biosensors

Inositol 1,4,5-trisphosphate (IP(3)) is an intracellular messenger that elicits a wide range of spatial and temporal Ca(2+) signals, and this signaling versatility is exploited to regulate diverse cellular responses. In the present study, we have developed a series of IP(3) biosensors that exhibit strong pH stability and varying affinities for IP(3), as well as a method for the quantitative measurement of cytosolic concentrations of IP(3) ([IP(3)](i)) in single living cells. We applied this method to elucidate IP(3) dynamics during agonist-induced Ca(2+) oscillations, and demonstrated cell type-dependent differences in IP(3) dynamics; a non-fluctuating rise in [IP(3)](i) and repetitive IP(3) spikes during Ca(2+) oscillations in COS-7 cells and HSY-EA1 cells, respectively. The size of the IP(3) spikes in HSY-EA1 cells varied from 10 to 100 nM, and the [IP(3)](i) spike peak was preceded by a Ca(2+) spike peak. These results suggest that repetitive IP(3) spikes in HSY-EA1 cells are passive reflections of Ca(2+) oscillations, and are unlikely to be essential for driving Ca(2+) oscillations. The novel method described herein as well as the quantitative information obtained by using this method should provide a valuable and sound basis for future studies on the spatial and temporal regulations of IP(3) and Ca(2+).

Monitoring of IP3 dynamics during the mechanical stimulation-induced intra- and intercellular Ca2+ waves in HSY human parotid cell line

It is well known that mechanical stimulation elicits Ca responses in various cell types. Touch stimulation on a single cell induces an increase in the cytosolic Ca concentration ([Ca]i), which subsequently propagates to neighboring cells as an intercellular Ca wave. In addition to Ca entry through mechanosensitive channels, this Ca response is thought to be induced, at least in part, by inositol 1,4,5-trisphosphate (IP3)-dependent Ca release from intracellular Ca stores (1-3). However, this hypothesis has not been tested directly due to a lack of the quantitative method to measure the cytosolic concentration of IP3 ([IP3]i) in a single living cell. Recently, we developed a FRET-based IP3 biosensor, LIBRAvIII, and a method to measure [IP3]i quantitatively in the single living cell (4). In order to examine the involvement of IP3 in mechanical stimulation-induced Ca responses, we monitored IP3 and Ca responses simultaneously in HSY-EA1 cells, a human parotid cell line, using LIBRAvIII and the Ca indicator fura-2.

Lysophospholipid Receptor-Mediated Calcium Signaling in Human Keratinocytes

The lysophospholipids, sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), stimulate chemotaxis and induce differentiation of human keratinocytes. As Ca(2+) plays an important role in keratinocyte differentiation, we studied Ca(2+) signaling by S1P and LPA in these cells, known to express mRNA transcripts of the S1P(1-5) and LPA(1-3) receptors, and the receptor subtypes involved in this process. S1P and LPA caused transient increases in intracellular free Ca(2+) concentration ([Ca(2+)](i)), with pEC(50) values of 8.5+/-0.11 and 7.5+/-0.23, respectively. The [Ca(2+)](i) increases are apparently mediated by stimulation of phospholipase C and involve Ca(2+) mobilization from thapsigargin-sensitive stores and subsequent Ca(2+) influx. The LPA-induced [Ca(2+)](i) increases were not inhibited by the LPA(1/3) receptor antagonist, dioctanoylglycerol pyrophosphate. The S1P-induced [Ca(2+)](i) increases were largely inhibited by the putative S1P(3) antagonist, BML-241, and the S1P(1/3) antagonist, VPC23019. The S1P(1)-specific agonist, SEW2871, did not increase [Ca(2+)](i) but stimulated chemotaxis of keratinocytes, which was fully blocked by S1P(1) antisense oligonucleotides. The data indicate that LPA and S1P potently increase [Ca(2+)](i) in human keratinocytes and that the effect of LPA is mediated by LPA(2), whereas that of S1P is mediated at least to a large part by S1P(3). The S1P(1) receptor, without stimulating [Ca(2+)](i) increases, mediates chemotaxis of keratinocytes.

Analysis of IP3 dynamics during the intracellular Ca2+ oscillations in mammalian eggs

Analysis of IP3 dynamics during the intracellular Ca2+ oscillations in mammalian eggs

A single-pool model for intracellular calcium oscillations and waves in the Xenopus laevis oocyte

We construct a minimal model of cytosolic free Ca2+ oscillations based on Ca2+ release via the inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ channel (IP3R) of a single intracellular Ca2+ pool. The model relies on experimental evidence that the cytosolic free calcium concentration ([Ca2+]c) modulates the IP3R in a biphasic manner, with Ca2+ release inhibited by low and high [Ca2+]c and facilitated by intermediate [Ca2+]c, and that channel inactivation occurs on a slower time scale than activation. The model produces [Ca2+]c oscillations at constant [IP3] and reproduces a number of crucial experiments. The two-dimensional spatial model with IP3 dynamics, cytosolic diffusion of IP3 (Dp = 300 microns 2 s-1), and cytosolic diffusion of Ca2+ (Dc = 20 microns 2 s-1) produces circular, planar, and spiral waves of Ca2+ with speeds of 7-15 microns.s-1, which annihilate upon collision. Increasing extracellular [Ca2+] influx increases wave speed and baseline [Ca2+]c. A [Ca2+]c-dependent Ca2+ diffusion coefficient does not alter the qualitative behavior of the model. An important model prediction is that channel inactivation must occur on a slower time scale than activation in order for waves to propagate. The model serves to capture the essential macroscopic mechanisms that are involved in the production of intracellular Ca2+ oscillations and traveling waves in the Xenopus laevis oocyte.