Fast calcium wave propagation mediated by electrically conducted excitation and boosted by CICR

2008 ◽  
Vol 294 (4) ◽  
pp. C917-C930 ◽  
Author(s):  
J. M. A. M. Kusters ◽  
W. P. M. van Meerwijk ◽  
D. L. Ypey ◽  
A. P. R. Theuvenet ◽  
C. C. A. M. Gielen
Keyword(s):  
Intracellular Calcium ◽  
Chloride Channels ◽  
Calcium Release ◽  
Rat Kidney ◽  
Electrical Coupling ◽  
Calcium Oscillations ◽  
Calcium Wave ◽  
Calcium Oscillation ◽  
Pacemaker Cell ◽  
Pacemaker Cells

We have investigated synchronization and propagation of calcium oscillations, mediated by gap junctional excitation transmission. For that purpose we used an experimentally based model of normal rat kidney (NRK) cells, electrically coupled in a one-dimensional configuration (linear strand). Fibroblasts such as NRK cells can form an excitable syncytium and generate spontaneous inositol 1,4,5-trisphosphate (IP3)-mediated intracellular calcium waves, which may spread over a monolayer culture in a coordinated fashion. An intracellular calcium oscillation in a pacemaker cell causes a membrane depolarization from within that cell via calcium-activated chloride channels, leading to an L-type calcium channel-based action potential (AP) in that cell. This AP is then transmitted to the electrically connected neighbor cell, and the calcium inflow during that transmitted AP triggers a calcium wave in that neighbor cell by opening of IP3 receptor channels, causing calcium-induced calcium release (CICR). In this way the calcium wave of the pacemaker cell is rapidly propagated by the electrically transmitted AP. Propagation of APs in a strand of cells depends on the number of terminal pacemaker cells, the L-type calcium conductance of the cells, and the electrical coupling between the cells. Our results show that the coupling between IP3-mediated calcium oscillations and AP firing provides a robust mechanism for fast propagation of activity across a network of cells, which is representative for many other cell types such as gastrointestinal cells, urethral cells, and pacemaker cells in the heart.

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

2020 ◽  
Vol 66 ◽  
pp. 150-156
Author(s):  
Peng-Fei Duan ◽  
Xi-Ping Yuan ◽  
Shu Gan ◽  
Yu Zhang ◽  
Wei-Long Duan
Keyword(s):  
Time Delay ◽  
Intracellular Calcium ◽  
Calcium Wave ◽  
Calcium Oscillation ◽  
Intracellular Calcium Oscillation

Laser backscatter studies of intracellular Ca2+ oscillations in isolated hearts

1989 ◽  
Vol 257 (2) ◽  
pp. H665-H673 ◽  
Author(s):  
M. D. Stern ◽  
H. F. Weisman ◽  
D. G. Renlund ◽  
G. Gerstenblith ◽  
O. Hano ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Release ◽  
Scattered Light ◽  
Calcium Oscillations ◽  
Extracellular Potassium ◽  
Base Line ◽  
Measured Intensity ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Intensity Fluctuations

We measured intensity fluctuations of 633 nm laser light backscattered from the epicardial surface of isolated, perfused rat and rabbit hearts. Scattered light intensity fluctuations (SLIF) were detected from verapamil-arrested rat hearts. The frequency of SLIF was increased by maneuvers that raise intracellular calcium. SLIF were abolished by removal of extracellular calcium with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and by blockade of sarcoplasmic reticulum calcium release by ryanodine. SLIF were not accompanied by any surface electro-cardiogram and were not abolished by 144 mM extracellular potassium. SLIF were absent in rabbit hearts under base-line conditions but could be provoked by calcium loading using zero potassium and ouabain. We conclude that backscatter SLIF monitor the microscopic motion caused by intracellular calcium oscillations in the intact heart. We measured SLIF from rat hearts during 60 min of global ischemia at 30 degrees C, followed by reflow. Ischemia reduced SLIF frequency to zero within 30 min. Reflow caused an overshoot of SLIF frequency to as much as five times control, suggesting that reflow causes major calcium overload of cells that are at least transiently viable.

Abstract 14219: Oxidation of PKA-RIα Protects Against Ischemia-reperfusion Injury by Inhibiting Lysosomal-triggered Calcium Release

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jillian N Simon ◽  
BESARTE VRELLAKU ◽  
Stefania Monterisi ◽  
Sandy Chu ◽  
Nadiia Rawlings ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Release ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Calcium Oscillations ◽  
Pore Channel ◽  
Calcium Stores ◽  
Potent Inducer ◽  
Disulfide Formation ◽  
The Impact

Introduction: Kinase oxidation is a critical signaling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, the regulatory Iα subunit of Protein Kinase A (PKARIα) can be reversibly oxidised, forming interprotein disulfide bonds within the holoenzyme complex. However, the impact of disulfide formation on kinase function, and its influence on PKA signaling in the context of heart disease remains unknown. Methods & Results: Myocardial ischemia-reperfusion (I/R) was found to be a potent inducer of PKARIα disulfide formation in vivo , both in mice and in humans. Using imaging modalities with high spatial and temporal resolution, we found that this conformation did not increase intrinsic PKA catalytic activity, but rather facilitated enhanced AKAP-dependent compartmentation of PKARIα in the adult mouse left ventricular (LV) myocyte, with preferential localization to the lysosome under oxidized conditions (n=38-41 myocytes, N=3 animals, p<0.01). Investigations in isolated LV myocytes revealed disulfide-modified PKARIα to be a significant regulator of lysosomal two pore channel (TPC)-dependent calcium-induced calcium release, with myocytes from ‘redox dead’ PKARIα mice (Cys17Ser) displaying spontaneous sarcoplasmic reticulum calcium release events and pronounced intracellular calcium oscillations. These events were prevented by ryanodine receptor blockade (1 mM tetracaine; n=14, p<0.01), acute depletion of lysosomal calcium stores (100 nM bafilomycin; n=7; p<0.01), or TPC inhibition (5 μM Ned-19; n=9; p<0.05). Absence of I/R-induced disulfide formation in “redox dead” PKARIα mouse hearts resulted in larger infarcts (2-fold increase, p<0.001) and a concomitant reduction in LV contractile recovery (1.6-fold, p<0.001), which could be fully prevented by administering the TPC inhibitor, Ned-19, at the time of reperfusion. Conclusions: Oxidised PKARIα acts as a potent inhibitor of intracellular calcium release in the heart through its redox-dependent interaction with the lysosome. In the setting of I/R, where PKA oxidation is induced, this regulatory mechanism is critical for protecting the heart from injury and offers a novel target for the design of cardioprotective therapeutics.

Modeling action potential generation and propagation in NRK fibroblasts

2004 ◽  
Vol 287 (4) ◽  
pp. C851-C865 ◽  
Author(s):  
J. J. Torres ◽  
L. N. Cornelisse ◽  
E. G. A. Harks ◽  
W. P. M. van Meerwijk ◽  
A. P. R. Theuvenet ◽  
...  
Keyword(s):  
Action Potential ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Cell Transformation ◽  
Rat Kidney ◽  
Potassium Conductance ◽  
Calcium Dynamics ◽  
Starting Point ◽  
Release Analysis ◽  
Intracellular Calcium Dynamics

Normal rat kidney (NRK) fibroblasts change their excitability properties through the various stages of cell proliferation. The present mathematical model has been developed to explain excitability of quiescent (serum deprived) NRK cells. It includes as cell membrane components, on the basis of patch-clamp experiments, an inwardly rectifying potassium conductance ( GKir), an L-type calcium conductance ( GCaL), a leak conductance ( Gleak), an intracellular calcium-activated chloride conductance [ GCl(Ca)], and a gap junctional conductance ( Ggj), coupling neighboring cells in a hexagonal pattern. This membrane model has been extended with simple intracellular calcium dynamics resulting from calcium entry via GCaL channels, intracellular buffering, and calcium extrusion. It reproduces excitability of single NRK cells and cell clusters and intercellular action potential (AP) propagation in NRK cell monolayers. Excitation can be evoked by electrical stimulation, external potassium-induced depolarization, or hormone-induced intracellular calcium release. Analysis shows the roles of the various ion channels in the ultralong (∼30 s) NRK cell AP and reveals the particular role of intracellular calcium dynamics in this AP. We support our earlier conclusion (De Roos A, Willems PH, van Zoelen EJ, and Theuvenet AP. Am J Physiol Cell Physiol 273: C1900–C1907, 1997) that AP generation and propagation may act as a rapid mechanism for the propagation of intracellular calcium waves, thus contributing to fast intercellular calcium signaling. The present model serves as a starting point to further analyze excitability changes during contact inhibition and cell transformation.

Soluble extracts from ascidian spermatozoa trigger intracellular calcium release independently of the activation of the ADP ribose channel

Zygote ◽  
1998 ◽  
Vol 6 (2) ◽  
pp. 149-154 ◽  
Author(s):  
Martin Wilding ◽  
Brian Dale
Keyword(s):  
Nitric Oxide ◽  
Plasma Membrane ◽  
Intracellular Calcium ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Calcium Release ◽  
Ciona Intestinalis ◽  
Calcium Transient ◽  
Calcium Oscillations ◽  
Repetitive Pattern

We have injected soluble extracts of sperm from the ascidian Ciona intestinalis into oocytes of the same species to test whether these extracts can mimic the events of fertilisation. Injection of ascidian sperm extracts leads, after a delay of approximately 60 s, to a large calcium transient and repetitive pattern of calcium oscillations, mimicking the normal fertilisation response. The response was concentration-independent, suggesting a stimulatory mechanism in triggering the fertilisation response. We tested the pathway of calcium release in ascidian oocytes after injection of sperm extracts by preinjection of calcium release inhibitors. The data demonstrate that dual pathways to calcium release act at fertilisation in ascidians, as in other species. C. intestinalis oocytes are characterised by a nion channel in the plasma membrane that is gated uniquely by ADP ribose. We show that this channel is not gated by the injection of ascidian sperm extracts. Our data suggest that one metabolic pathway triggered by sperm, the release of nitric oxide, is not stimulated by sperm extracts and that several metabolic pathways are stimulated at fertilisation by more than one factor within sperm.

Spatial and temporal aspects of cell signalling

1988 ◽  
Vol 320 (1199) ◽  
pp. 325-343 ◽  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Release ◽  
Cell Signalling ◽  
Calcium Signalling ◽  
Cell Types ◽  
Calcium Oscillations ◽  
Temporal Organization ◽  
Oscillatory Activity ◽  
Free Calcium ◽  
Inositol Lipids

As new techniques are developed to measure intracellular messengers it becomes increasingly apparent that there is a remarkable spatial and temporal organization of cell signalling. Cells possess a small discrete hormone-sensitive pool of inositol lipid. In some cells such as Xenopus oocytes and Limulus photoreceptors this phosphoinositide signalling system is highly concentrated in one region of the cell, so establishing localized calcium gradients. Another example is the hydrolysis of inositol lipids in eggs at the point of sperm entry resulting in a localized increase in Ins(1,4,5) P 3 and calcium which spreads like a wave throughout the egg. In hamster eggs this burst of calcium at fertilization recurs at 1-3 min intervals for over 100 min, a particularly dramatic example of spontaneous activity. Spontaneous oscillations in intracellular calcium exist in many different cell types and are often induced by agonists that hydrolyse inositol lipids. We have made a distinction between oscillations that are approximately sinusoidal and occur at a higher frequency where free calcium is probably continuously involved in the oscillatory cycle and those where calcium falls to resting levels for many seconds between transients. In the former case, the oscillations are thought to be induced through a cytoplasmic oscillator based on the phenomenon of calcium-induced calcium release. Such oscillations can be induced in Xenopus oocytes after injection with Ins(1,4,5) P 3 . A receptor-controlled oscillator based on the periodic formation of I ns (1,4,5) P 3 is probably responsible for the generation of the widely spaced calcium transients. The function of such calcium oscillations is currently unknown. They may be a reflection of the feedback interactions that operate to control intracellular calcium. Another possibility emerged from observations that in some cells the frequency of calcium oscillations varied with agonist concentration, suggesting that cells might employ these oscillations as a way of encoding information. One advantage of using such a frequency-dependent mechanism may lie in an increase in fidelity, especially at low agonist concentrations. Whatever these functions might be, it is clear that uncovering the mechanisms responsible for such oscillatory activity will greatly enhance our understanding of the relation between the phosphoinositides and calcium signalling.

Hopf Bifurcation and Numerical Simulation in a Calcium Oscillation Model

2012 ◽  
Vol 226-228 ◽  
pp. 510-515 ◽  
Author(s):  
Hong Kun Zuo ◽  
Quan Bao Ji ◽  
Yi Zhou
Keyword(s):  
Hopf Bifurcation ◽  
Intracellular Signaling ◽  
Calcium Release ◽  
Dimensional Space ◽  
Calcium Oscillations ◽  
Calcium Oscillation ◽  
Subcritical Hopf Bifurcation ◽  
Calcium Induced Calcium Release ◽  
Parameter Values ◽  
Centre Manifold Theorem

Calcium oscillations play a very important role in providing the intracellular signaling, and many mathematical models have been proposed to describe calcium oscillations. The Shen-Larter model presented here is based on calcium-induced calcium release (CICR) and the inositol trisphosphate cross-coupling (ICC). Nonlinear dynamics of this model is investigated by using the centre manifold theorem and bifurcation theory, including the variation in classification and stability of equilibria with different parameter values. The results show that the appearance and disappearance of calcium oscillations are due to subcritical Hopf bifurcation of equilibria. The numerical simulations are performed in order to illustrate the correctness of our theoretical analysis, including the bifurcation diagram of fixed points, the phase diagram of the system in two dimensional space and time series.

Complex Dynamics in the Kummer-Olsen Model of Calcium Oscillations

2012 ◽  
Vol 226-228 ◽  
pp. 505-509
Author(s):  
Zheng Fei Wu ◽  
Yi Zhou
Keyword(s):  
Theoretical Analysis ◽  
Calcium Release ◽  
Complex Dynamics ◽  
Cytosolic Calcium ◽  
Vital Role ◽  
Calcium Oscillations ◽  
Calcium Oscillation ◽  
Center Manifold Theorem ◽  
Oscillation Model ◽  
Calcium Induced Calcium Release

Oscillations of cytosolic calcium concentration, known as calcium oscillations, play a vital role in providing the intracellular signalling. These oscillations are explained with a model based on calcium-induced calcium release (CICR). The nonlinear dynamics of the Kummer-Olsen calcium oscillation model is discussed by using the center manifold theorem and bifurcation theory, including the variation in classification and stability of equilibria with parameter value. It is concluded that the appearance and disappearance of calcium oscillations in this system is due to supercritical Hopf bifurcation of equilibria. Finally, numerical simulations are carried out to support the theoretical analysis of the research. By combining the existing numerical results with the theoretical analysis results in this paper, a complete description of the dynamics of the Kummer-Olsen calcium oscillation model has now been obtained.

Dynamical Analysis of a Calcium Oscillation Model in Non-Excitable Cells

2012 ◽  
Vol 226-228 ◽  
pp. 521-525
Author(s):  
Yi Zhou ◽  
Zheng Fei Wu ◽  
Yu Hong Huo
Keyword(s):  
Calcium Release ◽  
Complex Dynamics ◽  
Calcium Oscillations ◽  
Dynamical Analysis ◽  
Phase Portraits ◽  
Calcium Oscillation ◽  
Stimulation Level ◽  
Time Courses ◽  
Stability And Bifurcations ◽  
Calcium Induced Calcium Release

The Borghans-Dupont model of calcium oscillations based on both the calcium-induced calcium release and calcium-activated inositol trisphosphate concentration degradation is considered. Dynamical effect of the stimulation level on the calcium oscillation behavior is studied. The qualitative theory of differential equations is used to explain the mechanism of these oscillations. We investigate the existence, types, stability and bifurcations of the equilibria by applying the centre manifold theorem, stability theory and bifurcation theory and prove that oscillations are due to supercritical Hopf bifurcation. Finally, we perform numerical simulations, including time courses, phase portraits and bifurcation diagram, to validate the correctness and the effectiveness of our theoretical analysis. These results may be instructive for understanding the role of the stimulation level played in complex dynamics in this model.

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