scholarly journals A mathematical model of spontaneous calcium release in cardiac myocytes

2011 ◽  
Vol 300 (5) ◽  
pp. H1794-H1805 ◽  
Author(s):  
Wei Chen ◽  
Gary Aistrup ◽  
J. Andrew Wasserstrom ◽  
Yohannes Shiferaw
Keyword(s):  
Mathematical Model ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Calcium Release ◽  
Cardiac Tissue ◽  
Ectopic Beat ◽  
Ionic Model ◽  
Triggered Activity ◽  
Voltage Dependent ◽  
Key Features

In cardiac myocytes, calcium (Ca) can be released from the sarcoplasmic reticulum independently of Ca influx from voltage-dependent membrane channels. This efflux of Ca, referred to as spontaneous Ca release (SCR), is due to Ryanodine receptor fluctuations, which can induce spontaneous Ca sparks, which propagate to form Ca waves. This release of Ca can then induce delayed after-depolarizations (DADs), which can lead to arrhythmogenic-triggered activity in the heart. However, despite its importance, to date there is no mathematical model of SCR that accounts for experimentally observed features of subcellular Ca. In this article, we present an experimentally based model of SCR that reproduces the timing distribution of spontaneous Ca sparks and key features of the propagation of Ca waves emanating from these spontaneous sparks. We have coupled this model to an ionic model for the rabbit ventricular action potential to simulate SCR within several thousand cells in cardiac tissue. We implement this model to study the formation of an ectopic beat on a cable of cells that exhibit SCR-induced DADs.

scholarly journals Sphingosylphosphocholine modulates the ryanodine receptor/calcium-release channel of cardiac sarcoplasmic reticulum membranes

1997 ◽  
Vol 322 (1) ◽  
pp. 327-333 ◽  
Author(s):  
Romeo BETTO ◽  
Alessandra TERESI ◽  
Federica TURCATO ◽  
Giovanni SALVIATI ◽  
Roger A. SABBADINI ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Calcium Release ◽  
Cardiac Tissue ◽  
Ruthenium Red ◽  
Release Mechanism ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Cardiac Sarcoplasmic Reticulum ◽  
High Calcium

Sphingosylphosphocholine (SPC) modulates Ca2+ release from isolated cardiac sarcoplasmic reticulum membranes; 50 ƁM SPC induces the release of 70Ő80% of the accumulated calcium. SPC releases calcium from cardiac sarcoplasmic reticulum through the ryanodine receptor, since the release is inhibited by the ryanodine receptor channel antagonists ryanodine, Ruthenium Red and sphingosine. In intact cardiac myocytes, even in the absence of extracellular calcium, SPC causes a rise in diastolic Ca2+, which is greatly reduced when the sarcoplasmic reticulum is depleted of Ca2+ by prior thapsigargin treatment. SPC action on the ryanodine receptor is Ca2+-dependent. SPC shifts to the left the Ca2+-dependence of [3H]ryanodine binding, but only at high pCa values, suggesting that SPC might increase the sensitivity to calcium of the Ca2+-induced Ca2+-release mechanism. At high calcium concentrations (pCa 4.0 or lower), where [3H]ryanodine binding is maximally stimulated, no effect of SPC is observed. We conclude that SPC releases calcium from cardiac sarcoplasmic reticulum membranes by activating the ryanodine receptor and possibly another intracellular Ca2+-release channel, the sphingolipid Ca2+-release-mediating protein of endoplasmic reticulum (SCaMPER) [Mao, Kim, Almenoff, Rudner, Kearney and Kindman (1996) Proc. Natl. Acad. Sci. U.S.A 93, 1993Ő1996], which we have identified for the first time in cardiac tissue.

scholarly journals Extracellular ATP-induced acidification leads to cytosolic calcium transient rise in single rat cardiac myocytes

1991 ◽  
Vol 274 (1) ◽  
pp. 55-62 ◽  
Author(s):  
M Pucéat ◽  
O Clément ◽  
F Scamps ◽  
G Vassort
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Membrane Conductance ◽  
Calcium Transient ◽  
Cytosolic Calcium ◽  
Extracellular Atp ◽  
Experimental Conditions ◽  
Extracellular Medium ◽  
Voltage Dependent ◽  
Ca2 Channels

The origin of the increase in cytosolic free Ca2+ concentration ([Ca2+]i) induced by extracellular ATP was investigated in single isolated cardiac myocytes loaded with indo-1. The nucleotide added at a concentration of 10 microM triggers a few Ca2+ spikes, followed by a cluster of Ca2+ oscillations, increasing [Ca2+]i to around 200 nM from a basal value of 70 nM. Neither caffeine nor ryanodine affects the magnitude of the Ca2+ transient, but both shorten it by preventing the Ca2+ oscillations. This indicates that the latter must be related to the release of Ca2+ from the sarcoplasmic reticulum. Since ATP also induces cell depolarization (as shown by experiments using the potential sensitive dye bis-oxonol), the initial Ca2+ spikes were attributed to the opening of voltage-dependent Ca2+ channels. A small Ca2+ transient still remains under experimental conditions designed to prevent Ca2+ influx from external medium (low-Ca2+ high-Mg2+ medium containing La3+) and after depletion of the sarcoplasmic-reticulum Ca2+ load with caffeine. Under these conditions, when this Ca2+ transient was buffered by 1,2-bis-(O-aminophenoxy)ethane-NNN′N′-tetra-acetic acid, ATP was unable to trigger the initial Ca2+ spikes. These results indicate that ATP mobilizes Ca2+ ions from an intracellular pool other than the sarcoplasmic reticulum and that this Ca2+ release is responsible for the depolarization. The effects of ATP on [Ca2+]i share the same characteristics as the acidification simultaneously induced by the nucleotide (as shown by experiments using the pH-sensitive probe snarf-1). These ionic variations are highly specific to ATP and its hydrolysis-resistant analogues. They both require the presence of Mg2+ and Cl- ions in the extracellular medium, and they are prevented by pretreatment of the cells with 4,4′-di-isothiocyanostilbene or probenecid. These results suggest that: (1) the ATP-induced acidification leads to displacement of Ca2+ ions from or close to the internal face of sarcolemma; (2) the Ca2+ ions activate a non-specific membrane conductance responsible for the depolarization of the cells; (3) the depolarization leads to a Ca2+ influx, owing to the opening of the voltage-dependent Ca2+ channels; (4) this increase in Ca2+ triggers the release of Ca2+ from the sarcoplasmic reticulum, which is facilitated by the increase in inositol trisphosphate following P2-purinergic stimulation.

scholarly journals Effects of rogue ryanodine receptors on Ca 2+ sparks in cardiac myocytes

2018 ◽  
Vol 5 (2) ◽  
pp. 171462 ◽  
Author(s):  
Xudong Chen ◽  
Yundi Feng ◽  
Yunlong Huo ◽  
Wenchang Tan
Keyword(s):  
Mathematical Model ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Ryanodine Receptors ◽  
Experimental Measurements ◽  
Release Mechanisms ◽  
Insight Into ◽  
Junctional Sarcoplasmic Reticulum

Ca 2+ sparks and Ca 2+ quarks, arising from clustered and rogue ryanodine receptors (RyRs), are significant Ca 2+ release events from the junctional sarcoplasmic reticulum (JSR). Based on the anomalous subdiffusion of Ca 2+ in the cytoplasm, a mathematical model was developed to investigate the effects of rogue RyRs on Ca 2+ sparks in cardiac myocytes. Ca 2+ quarks and sparks from the stochastic opening of rogue and clustered RyRs are numerically reproduced and agree with experimental measurements. It is found that the stochastic opening Ca 2+ release units (CRUs) of clustered RyRs are regulated by free Ca 2+ concentration in the JSR lumen (i.e. [Ca 2+ ] lumen ). The frequency of spontaneous Ca 2+ sparks is remarkably increased by the rogue RyRs opening at high [Ca 2+ ] lumen , but not at low [Ca 2+ ] lumen . Hence, the opening of rogue RyRs contributes to the formation of Ca 2+ sparks at high [Ca 2+ ] lumen . The interplay of Ca 2+ sparks and Ca 2+ quarks has been discussed in detail. This work is of significance to provide insight into understanding Ca 2+ release mechanisms in cardiac myocytes.

scholarly journals Ambiguous interactions between diastolic and SR Ca2+ in the regulation of cardiac Ca2+ release

2017 ◽  
Vol 149 (9) ◽  
pp. 847-855 ◽  
Author(s):  
Eric A. Sobie ◽  
George S.B. Williams ◽  
W.J. Lederer
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Calcium Release ◽  
Sarcoplasmic Reticulum Calcium

Sobie et al. highlight unresolved issues concerning the regulation of sarcoplasmic reticulum calcium release in cardiac myocytes.

scholarly journals Protein Phosphatases Decrease Sarcoplasmic Reticulum Calcium Content by Stimulating Calcium Release in Cardiac Myocytes

2003 ◽  
Vol 552 (1) ◽  
pp. 109-118 ◽  
Author(s):  
Dmitry Terentyev ◽  
Serge Viatchenko‐Karpinski ◽  
Inna Gyorke ◽  
Radmila Terentyeva ◽  
Sandor Gyorke
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Calcium Release ◽  
Protein Phosphatases ◽  
Calcium Content ◽  
Sarcoplasmic Reticulum Calcium

scholarly journals Spontaneous Ca2+ release from the sarcoplasmic reticulum limits Ca2+-dependent twitch potentiation in individual cardiac myocytes. A mechanism for maximum inotropy in the myocardium.

1988 ◽  
Vol 91 (1) ◽  
pp. 133-155 ◽  
Author(s):  
M C Capogrossi ◽  
M D Stern ◽  
H A Spurgeon ◽  
E G Lakatta
Keyword(s):  
Mathematical Model ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Total Cell ◽  
Inotropic Response ◽  
Twitch Potentiation ◽  
Intact Muscle ◽  
Rat Myocytes ◽  
Plausible Mechanism ◽  
In Cells

We hypothesized that the occurrence of spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), in diastole, might be a mechanism for the saturation of twitch potentiation common to a variety of inotropic perturbations that increase the total cell Ca. We used a videomicroscopic technique in single cardiac myocytes to quantify the amplitude of electrically stimulated twitches and to monitor the occurrence of the mechanical manifestation of spontaneous SR Ca2+ release, i.e., the spontaneous contractile wave. In rat myocytes exposed to increasing bathing [Ca2+] (Cao) from 0.25 to 10 mM, the Cao at which the peak twitch amplitude occurred in a given cell was not unique but varied with the rate of stimulation or the presence of drugs: in cells stimulated at 0.2 Hz in the absence of drugs, the maximum twitch amplitude occurred in 2 mM Cao; a brief exposure to 50 nM ryanodine before stimulation at 0.2 Hz shifted the Cao of the maximum twitch amplitude to 7 mM. In cells stimulated at 1 Hz in the absence of drugs, the maximum twitch amplitude occurred in 4 mM Cao; 1 microM isoproterenol shifted the Cao of the maximum twitch amplitude to 3 mM. Regardless of the drug or the stimulation frequency, the Cao at which the twitch amplitude saturated varied linearly with the Cao at which spontaneous Ca2+ release first occurred, and this relationship conformed to a line of identity (r = 0.90, p = less than 0.001, n = 25). The average peak twitch amplitude did not differ among these groups of cells. In other experiments, (a) the extent of rest potentiation of the twitch amplitude in rat myocytes was also limited by the occurrence of spontaneous Ca2+ release, and (b) in both rat and rabbit myocytes continuously stimulated in a given Cao, the twitch amplitude after the addition of ouabain saturated when spontaneous contractile waves first appeared between stimulated twitches. A mathematical model that incorporates this interaction between action potential-mediated SR Ca2+ release and the occurrence of spontaneous Ca2+ release in individual cells predicted the shape of the Cao-twitch relationship observed in other studies in intact muscle. Thus, the occurrence of spontaneous SR Ca2+ release is a plausible mechanism for the saturation of the inotropic response to Ca2+ in the intact myocardium.

scholarly journals Modulation of sarcoplasmic reticulum calcium release by calsequestrin in cardiac myocytes

2004 ◽  
Vol 37 (4) ◽  
Author(s):  
SANDOR GYÖRKE ◽  
INNA GYÖRKE ◽  
DMITRY TERENTYEV ◽  
SERGE VIATCHENKO-KARPINSKI ◽  
SIMON C WILLIAMS
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Calcium Release ◽  
Sarcoplasmic Reticulum Calcium

Spread of Ca2+ in the sarcomere during fast and slow activation of mammalian cardiac myocytes

2001 ◽  
Vol 79 (1) ◽  
pp. 82-86
Author(s):  
Masato Konishi ◽  
Yoichiro Kusakari ◽  
Kenichi Hongo ◽  
Satoshi Kurihara
Keyword(s):  
Mathematical Model ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Compartment Model ◽  
Mechanical Activity ◽  
Binding Reaction ◽  
The Mathematical Model ◽  
And Diffusion ◽  
Apparent Equilibrium

A multi-compartment model was used to estimate Ca2+ gradients in a sarcomere of a cardiac myocyte. The mathematical model assumed Ca2+ release from the sarcoplasmic reticulum as a driving function, and calculated Ca2+ binding to myoplasmic buffers, Ca2+ uptake by the sarcoplasmic reticulum, and diffusion of Ca2+ (and the buffers). During the fast Ca2+ transient similar to those observed during a twitch, the model predicted a large Ca2+ gradient in the sarcomere. A trajectory of the instantaneous relation between spatially averaged concentrations of Ca2+ and the Ca2+-troponin complex showed a counterclockwise loop, indicating non-equilibrium Ca2+ binding to troponin. During slow changes in [Ca2+] with time to peaks of ~500 ms or longer, the gradient of [Ca2+] was largely dissipated and the apparent equilibrium of the Ca2+-troponin binding reaction was suggested with little hysteresis of the trajectory. We conclude that a steady-state relation between [Ca2+] and mechanical activity can be achieved uniformly in the sarcomere by slowing the rate of Ca2+ release from the sarcoplasmic reticulum.Key words: calcium, troponin, cardiac myocytes, mathematical model.

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