Calcium Oscillations Research Articles

Evaluation of diagnostic accuracy of serum calcium channel \u03b12\u03b41 subunit in hepatocellular carcinoma-related cirrhosis

BackgroundHepatocellular carcinoma (HCC) is one of the commonest malignancies worldwide that carries a bad prognosis particularly in Egypt due to the high prevalence of HCV burden. Late diagnosis of HCC especially in cirrhosis suffering-liver is one of the causes that worsen HCC outcome. Identification of molecular pathways of HCC will open the gate for early diagnosis and effective management. Oscillation of calcium controlled by the α2δ1 subunit has been proposed as one of the mechanisms in tumor-initiating cell properties of HCC. In this study, we aim to evaluate the serum α2δ1 subunit level as a biological marker for HCC. A total of 90 participants were enrolled, 40 patients with HCC, 40 patients with cirrhosis, and 10 healthy volunteers; serum level of α2δ1 was assessed in all participants with ELISAResultsThe mean serum levels of α2δ1 were significantly higher in HCC group (19.53 ± 6.87 ng/dL) than cirrhotic (6.24 ± 2.64 ng/dL) and control groups (0.67 ± 0.48 ng/dL) (P = 0.001). There was no significance between α2δ1 and etiology of liver disease as viral (HCV, HBV) or non-viral (P = 0.14).Conclusionα2δ1 subunit may serve as a potential non-invasive marker with excellent sensitivity for diagnosis of HCC regardless of the etiology of liver disease.

Comparing 3D versus 2D intracellular calcium oscillations using high-throughput fluorescence measurement system (FDSS)

Comparing 3D versus 2D intracellular calcium oscillations using high-throughput fluorescence measurement system (FDSS)

Knockout of stim2a Increases Calcium Oscillations in Neurons and Induces Hyperactive-Like Phenotype in Zebrafish Larvae.

Stromal interaction molecule (STIM) proteins play a crucial role in store-operated calcium entry (SOCE) as endoplasmic reticulum Ca2+ sensors. In neurons, STIM2 was shown to have distinct functions from STIM1. However, its role in brain activity and behavior was not fully elucidated. The present study analyzed behavior in zebrafish (Danio rerio) that lacked stim2a. The mutant animals had no morphological abnormalities and were fertile. RNA-sequencing revealed alterations of the expression of transcription factor genes and several members of the calcium toolkit. Neuronal Ca2+ activity was measured in vivo in neurons that expressed the GCaMP5G sensor. Optic tectum neurons in stim2a−/− fish had more frequent Ca2+ signal oscillations compared with neurons in wildtype (WT) fish. We detected an increase in activity during the visual–motor response test, an increase in thigmotaxis in the open field test, and the disruption of phototaxis in the dark/light preference test in stim2a−/− mutants compared with WT. Both groups of animals reacted to glutamate and pentylenetetrazol with an increase in activity during the visual–motor response test, with no major differences between groups. Altogether, our results suggest that the hyperactive-like phenotype of stim2a−/− mutant zebrafish is caused by the dysregulation of Ca2+ homeostasis and signaling.

Effects of store-operated and receptor-operated calcium channels on synchronization of calcium oscillations in astrocytes

Intercellular calcium signaling allows cells to communicate with each other and to interact with adjacent cells. Gap junction is the most common and important way for cellular communication. Recently, mathematical models have been widely used to gain a precise and quantitative understanding of the dynamics of intracellular calcium ions (Ca2＋). In this paper, we establish a mathematical model considering the gap junction permeable to Ca2＋ and to IP3 for describing the calcium oscillations in coupled astrocytes. Store-operated calcium entry (SOCE) is viewed as the main process which controls the non-excitable cells, hence, we focus on the effect of store-operated calcium channel (SOCC) and receptor-operated calcium channel (ROCC) on the intercellular synchronization, respectively. By employing bifurcation analysis on this model, the dynamic behaviors of the coupled system with different physiological state cells is obtained with changes in the maximum capacity of the SOCC and the ROCC. The synchronization boundaries for different conditions are gained in the two parameters space of the channel parameters and the coupling strength. The results suggest that the variation of the maximum flow for different calcium channels determines the stable oscillations of the coupled system, as well as for the frequency and amplitude of oscillations. The SOCC has an expected effect on the change of the oscillatory interval while the ROCC demonstrated the influence on the amplitude modulation. Furthermore, the coupling strength and channel parameters could induce 1:1 locking of intercellular Ca2＋ oscillations and the synchronization region like Arnol’d tongue is found.

Kv10.1 Regulates Microtubule Dynamics during Mitosis.

Kv10.1 (potassium voltage-gated channel subfamily H member 1, known as EAG1 or Ether-à-go-go 1), is a voltage-gated potassium channel, prevailingly expressed in the central nervous system. The aberrant expression of Kv10.1 is detected in over 70% of all human tumor tissues and correlates with poorer prognosis. In peripheral tissues, Kv10.1 is expressed almost exclusively during the G2/M phase of the cell cycle and regulates its progression—downregulation of Kv10.1 extends the duration of the G2/M phase both in cancer and healthy cells. Here, using biochemical and imaging techniques, such as live-cell measurements of microtubule growth and of cytosolic calcium, we elucidate the mechanisms of Kv10.1-mediated regulation at the G2/M phase. We show that Kv10.1 has a dual effect on mitotic microtubule dynamics. Through the functional interaction with ORAI1 (calcium release-activated calcium channel protein 1), it modulates cytosolic calcium oscillations, thereby changing microtubule behavior. The inhibition of either Kv10.1 or ORAI1 stabilizes the microtubules. In contrast, the knockdown of Kv10.1 increases the dynamicity of mitotic microtubules, resulting in a stronger spindle assembly checkpoint, greater mitotic spindle angle, and a decrease in lagging chromosomes. Understanding of Kv10.1-mediated modulation of the microtubule architecture will help to comprehend how cancer tissue benefits from the presence of Kv10.1, and thereby increase the efficacy and safety of Kv10.1-directed therapeutic strategies.

Caloric restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination, and insulin secretion in prediabetic mice.

Caloric restriction can decrease the incidence of metabolic diseases, such as obesity and Type 2 diabetes mellitus. The mechanisms underlying the benefits of caloric restriction involved in insulin secretion and glucose homeostasis are not fully understood. Intercellular communication within the islets of Langerhans, mediated by Connexin36 (Cx36) gap junctions, regulates insulin secretion dynamics and glucose homeostasis. The goal of this study was to determine whether caloric restriction can protect against decreases in Cx36 gap junction coupling and altered islet function induced in models of obesity and prediabetes. C57BL6 mice were fed with a high-fat diet (HFD), showing indications of prediabetes after 2 mo, including weight gain, insulin resistance, and elevated fasting glucose and insulin levels. Subsequently, mice were submitted to 1 mo of 40% caloric restriction (2 g/day of HFD). Mice under 40% caloric restriction showed reversal in weight gain and recovered insulin sensitivity, fasting glucose, and insulin levels. In islets of mice fed the HFD, caloric restriction protected against obesity-induced decreases in gap junction coupling and preserved glucose-stimulated calcium signaling, including Ca2+ oscillation coordination and oscillation amplitude. Caloric restriction also promoted a slight increase in glucose metabolism, as measured by increased NAD(P)H autofluorescence, as well as recovering glucose-stimulated insulin secretion. We conclude that declines in Cx36 gap junction coupling that occur in obesity can be completely recovered by caloric restriction and obesity reversal, improving Ca2+ dynamics and insulin secretion regulation. This suggests a critical role for caloric restriction in the context of obesity to prevent islet dysfunction.

Calcium Oscillatory Patterns and Oocyte Activation During Fertilization: a Possible Mechanism for Total Fertilization Failure (TFF) in Human In Vitro Fertilization?

This paper reviews the effects of calcium oscillatory patterns in oocytes and early embryo development. Total fertilization failure (TFF) is the failure of fertilization in all oocytes in a human IVF cycle, even after treatment with intracytoplasmic sperm injection (ICSI). It is not well understood and currently attributed to oocyte activation deficiency. Calcium signaling is important in oocyte activation events. Calcium oscillations, in particular, have been reported in animal and human oocytes after fertilization. Abnormal calcium oscillations after fertilization may be the principal mechanism for TFF. While studies also establish strong associations between abnormal calcium oscillatory patterns and suboptimal developmental outcomes, critical basic parameters and their mechanism of action have yet to be identified. Empirical use of artificial oocyte activation (AOA) methods has shown initial success in helping patients overcome TFF. The AOA methods attempt to raise calcium levels after fertilization, but the efficacy and safety of these AOA methods are still in early stages of addressing TFF. Additional information about calcium oscillatory patterns and the effects of AOA in human ART may allow the prevention of TFF or allow treatment of TFF patients effectively and safely.

A Guard Cell Abscisic Acid (ABA) Network Model That Captures the Stomatal Resting State.

Stomatal pores play a central role in the control of carbon assimilation and plant water status. The guard cell pair that borders each pore integrates information from environmental and endogenous signals and accordingly swells or deflates, thereby increasing or decreasing the stomatal aperture. Prior research shows that there is a complex cellular network underlying this process. We have previously constructed a signal transduction network and a Boolean dynamic model describing stomatal closure in response to signals including the plant hormone abscisic acid (ABA), calcium or reactive oxygen species (ROS). Here, we improve the Boolean network model such that it captures the biologically expected response of the guard cell in the absence or following the removal of a closure-inducing signal such as ABA or external Ca2+. The expectation from the biological system is reversibility, i.e., the stomata should reopen after the closing signal is removed. We find that the model’s reversibility is obstructed by the previously assumed persistent activity of four nodes. By introducing time-dependent Boolean functions for these nodes, the model recapitulates stomatal reopening following the removal of a signal. The previous version of the model predicts ∼20% closure in the absence of any signal due to uncertainty regarding the initial conditions of multiple network nodes. We systematically test and adjust these initial conditions to find the minimally restrictive combinations that appropriately result in open stomata in the absence of a closure signal. We support these results by an analysis of the successive stabilization of feedback motifs in the network, illuminating the system’s dynamic progression toward the open or closed stomata state. This analysis particularly highlights the role of cytosolic calcium oscillations in causing and maintaining stomatal closure. Overall, we illustrate the strength of the Boolean network modeling framework to efficiently capture cellular phenotypes as emergent outcomes of intracellular biological processes.

Intercellular communication controls agonist-induced calcium oscillations independently of gap junctions in smooth muscle cells.

In this study, we report the existence of a communication system among human smooth muscle cells that uses mechanical forces to frequency modulate long-range calcium waves. An important consequence of this mechanical signaling is that changes in stiffness of the underlying extracellular matrix can interfere with the frequency modulation of Ca2+ waves, causing smooth muscle cells from healthy human donors to falsely perceive a much higher agonist dose than they actually received. This aberrant sensing of contractile agonist dose on stiffer matrices is completely absent in isolated smooth muscle cells, although the isolated cells can sense matrix rigidity. We show that the intercellular communication that enables this collective Ca2+ response in smooth muscle cells does not involve transport across gap junctions or extracellular diffusion of signaling molecules. Instead, our data support a collective model in which mechanical signaling among smooth muscle cells regulates their response to contractile agonists.

Abstract MP120: Ryanodine Receptor 2 Prevents Endoplasmic Reticulum Stress-induced Defects in Cardiomyocyte Maturation

Cardiomyocyte (CM) maturation is an essential step in heart development that prepares the organ for robust and sustainable contractions. However, very little is known about the contribution of CM maturation to cardiac pathogenesis, partly due to the paucity of basic knowledge about maturation. For example, although calcium plays well-established roles in cardiac stress responses, whether normal calcium oscillations are required for CM maturation has not been examined. To address this question, we created mice with mosaic inactivation of ryanodine receptor 2 (RYR2), the central channel that mediates calcium release from sarcoplasmic/endoplasmic reticulum (SR/ER), in CMs. RYR2 was depleted in a small fraction of neonatal CMs by adeno-associated virus (AAV)-mediated Cas9-based somatic mutagenesis (CASAAV). The majority of CMs intentionally retained RYR2 expression, which circumvented cardiac dysfunction and death that would result from widespread calcium transient ablation. In RYR2-depleted CMs, sarcomere expansion, transverse-tubule formation, mitochondrial metabolism and maturational hypertrophy were impaired. Strikingly, these maturation defects were associated with unfolded protein response, with the activation of three major ER stress effectors: spliced Xbp1 (XBP1s), ATF6 N-terminus (ATF6N), and ATF4. Tauroursodeoxycholic acid, an ER stress-relieving drug, partially rescued the maturation defects in RYR2-depleted CMs. Over expression (OE) of XBP1s, ATF6N or ATF4 each impaired CM maturation, with phenotypic severity ranked as ATF4>XBP1s>ATF6N. ATF4 OE in neonatal CMs triggered both ultrastructural and transcriptomic changes highly correlated with RYR2 depletion phenotypes. Interestingly, ATF4 OE altered distinct transcriptomic programs in neonatal vs. adult CMs and caused ultrastructural defects only at the neonatal stage. No terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was detected upon RYR2 depletion or ATF4 OE, excluding the contribution of apoptosis to maturation defects. Collectively, these data indicate that RYR2-mediated calcium handling prevents an adverse and stage-specific impact of ER stress on CM maturation, which lead to CM dysfunction.

Ionomycin-induced mouse oocyte activation can disrupt preimplantation embryo development through increased reactive oxygen species reaction and DNA damage

Oocyte activation induced by calcium oscillations is an important process in normal fertilization and subsequent embryogenesis. In the clinical-assisted reproduction, artificial oocyte activation (AOA) is an effective method to improve the clinical outcome of patients with null or low fertilization rate after ICSI. However, little is known about the effect of AOA on preimplantation embryo development in cases with normal fertilization by ICSI. Here, we used ionomycin at different concentrations to activate oocytes after ICSI with normal sperm and evaluated energy metabolism and preimplantation embryo development. We found that a high concentration of ionomycin increased the frequency and amplitude of calcium oscillation patterns, affecting the balance of mitochondrial energy metabolism, leading to increased reactive oxygen species (ROS) and decreased ATP. Eventually, it increases DNA damage and decreases blastocyst formation. In addition, the addition of vitamin C to the culture medium ameliorated the increase in ROS and DNA damage and rescued the abnormal embryo development caused by excessive ionomycin activation. This study provides a perspective that the improper application of AOA may have adverse effects on preimplantation embryo development. Thus, clinical AOA treatment should be cautiously administered.

MG53 suppresses interferon-\u03b2 and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling

TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and is believed to be a muscle-specific TRIM protein. Here we show human macrophages express MG53, and MG53 protein expression is reduced following virus infection. Knockdown of MG53 in macrophages leads to increases in type I interferon (IFN) upon infection. MG53 knockout mice infected with influenza virus show comparable influenza virus titres to wild type mice, but display increased morbidity accompanied by more accumulation of CD45+ cells and elevation of IFNβ in the lung. We find that MG53 knockdown results in activation of NFκB signalling, which is linked to an increase in intracellular calcium oscillation mediated by ryanodine receptor (RyR). MG53 inhibits IFNβ induction in an RyR-dependent manner. This study establishes MG53 as a new target for control of virus-induced morbidity and tissue injury.

Three-dimensional imaging and quantification of real-time cytosolic calcium oscillations in microglial cells cultured on electrospun matrices using laser scanning confocal microscopy.

The development of a minimally invasive, robust, and inexpensive technique that permits real-time monitoring of cell responses on biomaterial scaffolds can improve the eventual outcomes of scaffold-based tissue engineering strategies. Towards establishing correlations between in situ biological activity and cell fate, we have developed a comprehensive workflow for real-time volumetric imaging of spatiotemporally varying cytosolic calcium oscillations in pure microglial cells cultured on electrospun meshes. Live HMC3 cells on randomly oriented electrospun fibers were stained with a fluorescent dye and imaged using a laser scanning confocal microscope. Resonance scanning provided high-resolution in obtaining the time-course of intracellular calcium levels without compromising spatial and temporal resolution. Three-dimensional reconstruction and depth-coding enabled the visualization of cell location and intracellular calcium levels as a function of sample thickness. Importantly, changes in cell morphology and in situ calcium spiking were quantified in response to a soluble biochemical cue and varying matrix architectures (i.e., randomly oriented and aligned fibers). Importantly, raster plots generated from spiking data revealed calcium signatures specific to culture conditions. In the future, our approach can be used to elucidate correlations between calcium signatures and cell phenotype/activation, and facilitate the rational design of scaffolds for biomedical applications.

Dual mechanisms of Ca2+ oscillations in hepatocytes

Calcium (Ca2+) oscillations in hepatocytes control many critical cellular functions, including glucose metabolism and bile secretion. The mechanisms underlying repetitive Ca2+ oscillations and how these mechanisms regulate these oscillations is not fully understood. Recent experimental evidence has shown that both Ca2+ regulation of the inositol 1,4,5-trisphosphate (IP3) receptor and IP3 metabolism generate Ca2+ oscillations and co-exist in hepatocytes. To investigate the effects of these feedback mechanisms on the Ca2+ response, we construct a mathematical model of the Ca2+ signalling network in hepatocytes. The model accounts for the biphasic regulation of Ca2+ on the IP3 receptor (IP3R) and the positive feedback from Ca2+ on IP3 metabolism, via activation of phospholipase C (PLC) by agonist and Ca2+. Model simulations show that Ca2+ oscillations exist for both constant [IP3] and for [IP3] changing dynamically. We show, both experimentally and in the model, that as agonist concentration increases, Ca2+ oscillations transition between simple narrow-spike oscillations and complex broad-spike oscillations. The model predicts that narrow-spike oscillations persist when Ca2+ transport across the plasma membrane is blocked. This prediction has been experimentally validated. In contrast, broad-spike oscillations are terminated when plasma membrane transport is blocked. We conclude that multiple feedback mechanisms participate in regulating Ca2+ oscillations in hepatocytes.

Neobavaisoflavone inhibits osteoclastogenesis through blocking RANKL signalling-mediated TRAF6 and c-Src recruitment and NF-κB, MAPK and Akt pathways.

Psoralea corylifolia (P corylifolia) has been popularly applied in traditional Chinese medicine decoction for treating osteoporosis and promoting fracture healing since centuries ago. However, the bioactive natural components remain unknown. In this study, applying comprehensive two‐dimensional cell membrane chromatographic/C18 column/time‐of‐flight mass spectrometry (2D CMC/C18 column/TOFMS) system, neobavaisoflavone (NBIF), for the first time, was identified for the bioaffinity with RAW 264.7 cells membranes from the extracts of P corylifolia. Here, we revealed that NBIF inhibited RANKL‐mediated osteoclastogenesis in bone marrow monocytes (BMMCs) and RAW264.7 cells dose dependently at the early stage. Moreover, NBIF inhibited osteoclasts function demonstrated by actin ring formation assay and pit‐formation assay. With regard to the underlying molecular mechanism, co‐immunoprecipitation showed that both the interactions of RANK with TRAF6 and with c‐Src were disrupted. In addition, NBIF inhibited the phosphorylation of P50, P65, IκB in NF‐κB pathway, ERK, JNK, P38 in MAPKs pathway, AKT in Akt pathway, accompanied with a blockade of calcium oscillation and inactivation of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In vivo, NBIF inhibited osteoclastogenesis, promoted osteogenesis and ameliorated bone loss in ovariectomized mice. In summary, P corylifolia‐derived NBIF inhibited RANKL‐mediated osteoclastogenesis by suppressing the recruitment of TRAF6 and c‐Src to RANK, inactivating NF‐κB, MAPKs, and Akt signalling pathways and inhibiting calcium oscillation and NFATc1 translocation. NBIF might serve as a promising candidate for the treatment of osteoclast‐associated osteopenic diseases.

Calcium spikes, waves and oscillations in plant development and biotic interactions.

The calcium ion (Ca2+) is a universal signal in all eukaryotic cells. A fundamental question is how Ca2+, a simple cation, encodes complex information with high specificity. Extensive research has established a two-step process (encoding and decoding) that governs the specificity of Ca2+ signals. While the encoding mechanism entails a complex array of channels and transporters, the decoding process features a number of Ca2+ sensors and effectors that convert Ca2+ signals into cellular effects. Along this general paradigm, some signalling components may be highly conserved, but others are divergent among different organisms. In plant cells, Ca2+ participates in numerous signalling processes, and here we focus on the latest discoveries on Ca2+-encoding mechanisms in development and biotic interactions. In particular, we use examples such as polarized cell growth of pollen tube and root hair in which tip-focused Ca2+ oscillations specify the signalling events for rapid cell elongation. In plant-microbe interactions, Ca2+ spiking and oscillations hold the key to signalling specificity: while pathogens elicit cytoplasmic spiking, symbiotic microorganisms trigger nuclear Ca2+ oscillations. Herbivore attacks or mechanical wounding can trigger Ca2+ waves traveling a long distance to transmit and convert the local signal to a systemic defence program in the whole plant. What channels and transporters work together to carve out the spatial and temporal patterns of the Ca2+ fluctuations? This question has remained enigmatic for decades until recent studies uncovered Ca2+ channels that orchestrate specific Ca2+ signatures in each of these processes. Future work will further expand the toolkit for Ca2+-encoding mechanisms and place Ca2+ signalling steps into larger signalling networks.

Role of calcium-sensing receptor in cadmium-induced apoptosis of rat primary osteoblasts in vitro

Calcium is essential to various physiological and pathophysiological cellular processes. Calcium-sensing receptor (CasR), a seven-transmembrane-spanning protein that responds to changes in extracellular Ca2+, partly modulates calcium homeostasis, thereby influencing bone metabolism. In this study, we aimed to elucidate the role of CasR in Cd-induced calcium homeostasis disruption and OB apoptosis, and the underlying mechanisms. Cd treatment dramatically increased the protein expression of CasR and elevated the intracellular calcium concentration. Meanwhile, OBs apoptosis rate and caspase-dependent apoptosis protein levels, including cleaved caspase 3, cleaved caspase 9 and the ratio of Bax/Bcl-2 were increased. However, downregulation of CasR by CasR siRNA effectively suppressed the effects of Cd on theses phenomena. At the same time, we illustrated that CasR siRNA pretreatment blocked Cd-inhibited the phosphorylation of PKC and decreased Cd-induced the phosphorylation of PI3K/AKT.Our results suggested that CasR-mediated PKC and PI3K/AKT signaling pathways involve in calcium oscillation and apoptosis in OB caused by Cd maybe responsible for the bone homeostasis.

Contribution of NAADP to Glutamate-Evoked Changes in Ca2+ Homeostasis in Mouse Hippocampal Neurons.

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that evokes calcium release from intracellular organelles by the engagement of calcium release channels, including members of the Transient Receptor Potential (TRP) family, such as TRPML1, the (structurally) related Two Pore Channel type 1 (TPC1) and TPC2 channels as well as Ryanodine Receptors type 1 (RYR1; Guse, 2012). NAADP evokes calcium release from acidic calcium stores of many cell types (Guse, 2012), and NAADP-sensitive Ca2+ stores have been described in hippocampal neurons of the rat (Bak et al., 1999; McGuinness et al., 2007). Glutamate triggers Ca2+-mediated neuronal excitotoxicity in inflammation-induced neurodegenerative pathologies such as Multiple Sclerosis (MS; Friese et al., 2014), and when applied extracellularly to neurons glutamate can elevate NAADP levels in these cells. Accordingly, glutamate-evoked Ca2+ signals from intracellular organelles were inhibited by preventing organelle acidification (Pandey et al., 2009). Analysis of reported RNA sequencing experiments of cultured hippocampal neurons revealed the abundance of Mcoln1 (encoding TRPML1), Tpcn1, and Tpcn2 (encoding TPC1 and TPC2, respectively) as potential NAADP target channels in these cells. Transcripts encoding Ryr1 were not found in contrast to Ryr2 and Ryr3. To study the contribution of NAADP signaling to glutamate-evoked calcium transients in murine hippocampal neurons we used the NAADP antagonists Ned-19 (Naylor et al., 2009) and BZ194 (Dammermann et al., 2009). Our results show that both NAADP antagonists significantly reduce glutamate-evoked calcium transients. In addition to extracellular glutamate application, we studied synchronized calcium oscillations in the cells of the neuronal cultures evoked by addition of the GABAA receptor antagonist bicuculline. Pretreatment with Ned-19 (50 μM) or BZ194 (100 μM) led to an increase in the frequency of bicuculline-induced calcium oscillations at the cost of calcium transient amplitudes. Interestingly, Ned-19 triggered a rise in intracellular calcium concentrations 25 min after bicuculline stimulation, leading to the question whether NAADP acts as a neuroprotective messenger in hippocampal neurons. Taken together, our results are in agreement with the concept that NAADP signaling significantly contributes to glutamate evoked Ca2+ rise in hippocampal neurons and to the amplitude and frequency of synchronized Ca2+ oscillations triggered by spontaneous glutamate release events.

Time delay induces saw-tooth calcium wave and transition in intracellular calcium oscillation

In view of same time delay τ in active and passive transport processes of intracellular Ca2+ with additive Gaussian colored noise, using second-order algorithm for stochastic simulation colored noise, intracellular calcium oscillation (ICO) is investigated. By researching the time series and stationary probability distribution (SPD) of intracellular Ca2+ concentrations, take modest strength and enough long correlation time of additive colored noise, the results indicate that: time delay has a critical point τc ≃ 0.1s of time coherence, as τ > τc, ICO become periodical oscillation, and the waveform converts slowly into square wave from saw-tooth calcium wave as time delay further increases. Additionally, ICO system appears transition from monostable state to bistable state as time delay increases.

Astrocyte-induced intermittent synchronization of neurons in a minimal network

Abstract We investigate the impact of mixed coupling on synchronization in a minimal multiplex neuro-astrocytal ensemble, inspired by physiological systems. We find that calcium activity in astrocytes can effectively mediate neural interactions and control cooperative dynamics of neurons. In particular, astrocytes can induce the intermittent synchronization of a pair synaptically coupled fast spiking Hodgkin-Huxley neurons on the slow timescale of calcium oscillations.