scholarly journals Calcium Sparks in Cardiac Cells in Silico

2017 ◽  
Author(s):  
Alexander Ryvkin ◽  
N.S. Markov
Keyword(s):  
Calcium Release ◽  
Stochastic Dynamics ◽  
Computer Experiments ◽  
Cardiac Cells ◽  
Calcium Dynamics ◽  
Release Process ◽  
Calcium Diffusion ◽  
Dyadic Space ◽  
Conformational Model ◽  
Calcium Induced Calcium Release

We simulate elementary calcium release events (sparks) in a single calcium release unit in ventricular myocyte. Previously developed and tested electron-conformational model of the stochastic dynamics of RyR-channels is integrated to the calcium dynamics model in the cardiac cell. This approach allows to observe RyRs opening/closing in details on the macromolecular level during the calcium dynamics course. We simulate calcium diffusion in the dyadic space and “domino-like” RyR’s activation during the so-called “calcium induced-calcium release process”. Ca2+ sparks initiation, spread and termination are investigated in the computer experiments. Sparks’ initiation and termination rate dependence on the Ca2+ diffusion velocity is observed. We show that sarcoplasmic reticulum lumen local depletion and RyR’s stochastic attrition could be the reasons of Ca2+ spark termination.

Persistent current oscillations produced by activation of metabotropic glutamate receptors in immature rat CA3 hippocampal neurons

1995 ◽  
Vol 73 (4) ◽  
pp. 1422-1429 ◽  
Author(s):  
L. Aniksztejn ◽  
M. Sciancalepore ◽  
Y. Ben Ari ◽  
E. Cherubini
Keyword(s):  
Glutamate Receptors ◽  
Hippocampal Neurons ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Release ◽  
Release Process ◽  
Metabotropic Glutamate ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Presynaptic Nerve Terminals ◽  
Calcium Induced Calcium Release

1. The single-electrode voltage-clamp technique was used to study the effects of the metabotropic glutamate receptors (mGluRs) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, ACPD, 3-10 microM) on CA3 hippocampal neurons during the 1st 10 days of postnatal (P) life and in adulthood. 2. Repeated applications of 1S,3R-ACPD, in the presence of tetrodotoxin (TTX, 1 microM), tetraethylammonium chloride (TEACl 10 mM), and CsCl (2 mM), induced in immature but not in adult neurons periodic inward currents (PICs) that persisted for several hours after the last application of the agonist. 3. PICs, which were generated by nonspecific cationic currents, reversed polarity at 2.8 +/- 3 (SD) mV. They were reversibly blocked by kynurenic acid (1 mM), suggesting that they were mediated by glutamate acting on ionotropic receptors. They were also abolished in a nominally Ca(2+)-free medium. 4. PICs were irreversibly abolished by thapsigargin (10 microM) but were unaffected by ryanodine (10-40 microM). Caffeine (2 mM) also reversibly blocked PICs; this effect was independent from adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, inhibition of voltage-dependent Ca2+ current, or blockade of adenosine receptors. 5. We suggest that, in neonatal slices, mGluRs-induced PICs are triggered by elevation of [Ca2+]i, after mobilization of Ca2+ from inositol 1,4,5-trisphosphate (InsP3)-sensitive stores. This will lead to a persistent, pulsatile release of glutamate from presynaptic nerve terminals, a phenomenon that is probably maintained via a calcium-induced-calcium release process.

scholarly journals Local Control Models of Cardiac Excitation–Contraction Coupling

1999 ◽  
Vol 113 (3) ◽  
pp. 469-489 ◽  
Author(s):  
Michael D. Stern ◽  
Long-Sheng Song ◽  
Heping Cheng ◽  
James S.K. Sham ◽  
Huang Tian Yang ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Calcium Binding ◽  
Calcium Release ◽  
Stochastic Dynamics ◽  
Single Channel ◽  
Channel Measurements ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Calcium Induced Calcium Release ◽  
Gating Scheme

In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation–contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation–contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution.

scholarly journals A model of propagating calcium-induced calcium release mediated by calcium diffusion.

1989 ◽  
Vol 93 (5) ◽  
pp. 963-977 ◽  
Author(s):  
P H Backx ◽  
P P de Tombe ◽  
J H Van Deen ◽  
B J Mulder ◽  
H E ter Keurs
Keyword(s):  
Calcium Release ◽  
Cardiac Cells ◽  
Calcium Handling ◽  
Coupled Equations ◽  
Local Fluctuations ◽  
Calcium Loading ◽  
Method Of Solution ◽  
Spatial Coordinates ◽  
Predictor Corrector ◽  
Calcium Induced Calcium Release

The effect of sudden local fluctuations of the free sarcoplasmic [Ca++]i in cardiac cells on calcium release and calcium uptake by the sarcoplasmic reticulum (SR) was calculated with the aid of a simplified model of SR calcium handling. The model was used to evaluate whether propagation of calcium transients and the range of propagation velocities observed experimentally (0.05-15 mm s(-1)) could be predicted. Calcium fluctuations propagate by virtue of focal calcium release from the SR, diffusion through the cytosol (which is modulated by binding to troponin and calmodulin and sequestration by the SR), and subsequently induce calcium release from adjacent release sites of the SR. The minimal and maximal velocities derived from the simulation were 0.09 and 15 mm s(-1) respectively. The method of solution involved writing the diffusion equation as a difference equation in the spatial coordinates. Thus, coupled ordinary differential equations in time with banded coefficients were generated. The coupled equations were solved using Gear's sixth order predictor-corrector algorithm for stiff equations with reflective boundaries. The most important determinants of the velocity of propagation of the calcium waves were the diastolic [Ca++]i, the rate of rise of the release, and the amount of calcium released from the SR. The results are consistent with the assumptions that calcium loading causes an increase in intracellular calcium and calcium in the SR, and an increase in the amount and rate of calcium released. These two effects combine to increase the propagation velocity at higher levels of calcium loading.

Sarcomere motion in isolated cardiac cells

1979 ◽  
Vol 236 (1) ◽  
pp. C70-C77 ◽  
Author(s):  
G. Rieser ◽  
R. Sabbadini ◽  
P. Paolini ◽  
M. Fry ◽  
G. Inesi
Keyword(s):  
Image Analysis ◽  
Time Course ◽  
Calcium Release ◽  
Video Camera ◽  
Cardiac Cells ◽  
Adult Rabbit ◽  
Yield Data ◽  
Computerized Image Analysis ◽  
Dissociated Cells ◽  
Calcium Induced Calcium Release

Computerized image-analysis techniques have been employed to examine the sarcomere dynamics of isolated mammalian cardiac myocytes. The cells were prepared by perfusion of adult rabbit hearts with hyaluronidase-collagenase solutions; they exhibited phasic contractions in the presence of 10(-6) M Ca2+. The dissociated cells were visualized by phase microscopy and a video camera interfaced in a minicomputer. Digitized cell images were processed by an algorithm utilizing signal averaging and contrast enhancement to yield data showing individual sarcomere position and shortening vs. time, so that patterns of sarcomere activation could be observed in spontaneously contracting cells. Compared to records of whole-cell shortening and of striation displacement, computerized image analysis provided a much more faithful indication of time course and sequence of sarcomere shortening. Spontaneously contracting cells showed sequential sarcomere shortening beginning at one end and propagating longitudinally with a constant velocity, typically at 100--150 micron/s for beat rates of 40 min-1. Velocities of initial sarcomere shortening appeared to increase with elevated Ca2+. These observations are consistent with a regenerative mechanism of calcium-induced calcium release.

scholarly journals Model of calcium-induced calcium release mechanism in cardiac cells

1992 ◽  
Vol 54 (1) ◽  
pp. 95-116 ◽  
Author(s):  
Alan Y. K. Wong ◽  
Alexandre Fabiato ◽  
James B. Bassingthwaighthe
Keyword(s):  
Calcium Release ◽  
Cardiac Cells ◽  
Release Mechanism ◽  
Calcium Induced Calcium Release

Calcium-induced calcium release activates contraction in intact cardiac cells

1989 ◽  
Vol 413 (6) ◽  
pp. 676-678 ◽  
Author(s):  
M. Valdeolmillos ◽  
S. C. O'Neill ◽  
G. L. Smith ◽  
D. A. Eisner
Keyword(s):  
Calcium Release ◽  
Cardiac Cells ◽  
Calcium Induced Calcium Release

scholarly journals Postoperative malignant hyperthermia confirmed by calcium-induced calcium release rate after breast cancer surgery, in which prompt recognition and immediate dantrolene administration were life-saving: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Natsumi Miyazaki ◽  
Takayuki Kobayashi ◽  
Takako Komiya ◽  
Toshio Okada ◽  
Yusuke Ishida ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Temperature ◽  
Malignant Hyperthermia ◽  
Muscle Biopsy ◽  
Release Rate ◽  
Calcium Release ◽  
Cancer Surgery ◽  
Breast Cancer Surgery ◽  
Body Cooling ◽  
Calcium Induced Calcium Release

Abstract Background Malignant hyperthermia (MH) is a rare genetic disease characterized by the development of very serious symptoms, and hence prompt and appropriate treatment is required. However, postoperative MH is very rare, representing only 1.9% of cases as reported in the North American Malignant Hyperthermia Registry (NAMHR). We report a rare case of a patient who developed sudden postoperative hyperthermia after mastectomy, which was definitively diagnosed as MH by the calcium-induced calcium release rate (CICR) measurement test. Case presentation A 61-year-old Japanese woman with a history of stroke was hospitalized for breast cancer surgery. General anesthesia was introduced by propofol, remifentanil, and rocuronium. After intubation, anesthesia was maintained using propofol and remifentanil, and mastectomy and muscle flap reconstruction surgery was performed and completed without any major problems. After confirming her spontaneous breathing, sugammadex was administered and she was extubated. Thereafter, systemic shivering and masseter spasm appeared, and a rapid increase in body temperature (maximum: 38.9 °C) and end-tidal carbon dioxide (ETCO2) (maximum: 59 mmHg) was noted. We suspected MH and started cooling the body surface of the axilla, cervix, and body trunk, and administered chilled potassium-free fluid and dantrolene. After her body temperature dropped and her shivering improved, dantrolene administration was ended, and finally she was taken to the intensive care unit (ICU). Body cooling was continued within the target range of 36–37 °C in the ICU. No consciousness disorder, hypotension, increased serum potassium level, metabolic acidosis, or cola-colored urine was observed during her ICU stay. Subsequently, her general condition improved and she was discharged on day 12. Muscle biopsy after discharge was performed and provided a definitive diagnosis of MH. Conclusions The occurrence of MH can be life-threatening, but its frequency is very low, and genetic testing and muscle biopsy are required to confirm the diagnosis. On retrospective evaluation using the malignant hyperthermia scale, the present case was almost certainly that of a patient with MH. Prompt recognition and immediate treatment with dantrolene administration and body cooling effectively reversed a potentially fatal syndrome. This was hence a valuable case of a patient with postoperative MH that led to a confirmed diagnosis by CICR.

A SIMPLE MODEL FOR INTERACTION OF VOLTAGE AND CALCIUM DYNAMICS IN VIRTUAL VENTRICULAR TISSUE

2003 ◽  
Vol 13 (12) ◽  
pp. 3873-3886
Author(s):  
O. V. ASLANIDI ◽  
A. V. HOLDEN
Keyword(s):  
Intracellular Calcium ◽  
Calcium Release ◽  
Cell Model ◽  
Excitation Threshold ◽  
Calcium Dynamics ◽  
Variable Model ◽  
Ventricular Cell ◽  
Calcium Dependent ◽  
Intracellular Ca ◽  
A Site

A simple two-variable model is used to replace the formulation of calcium dynamics in the Luo–Rudy ventricular cell model. Virtual ventricular cell and tissue are developed and validated to reproduce restitution properties and calcium-dependent voltage patterns present in the original model. Basic interactions between the membrane potential and Ca 2+ dynamics in the virtual cell and a strand of the virtual tissue are studied. Intracellular calcium waves can be linked to both action potentials (APs) and delayed afterdepolarizations (DADs). An intracellular calcium wave propagating from the cell interior can induce an AP upon reaching the cell membrane. The voltage and the intracellular Ca 2+ patterns within the same cell can be highly desynchronized. In a one-dimensional strand of the virtual tissue calcium motion is driven by the AP propagation. However, calcium release can be induced upon certain conditions (e.g. Na + overload of the cells), which results in DADs propagating in the wake of AP. Such propagating DADs can reach the excitation threshold, generating a pair of extrasystolic APs. Collision of a propagating AP with a site of elevated intracellular Ca 2+ concentration does not affect the propagation under the normal conditions. Under Na + overload local elevation of the intracellular Ca 2+ leads to generation of an extrasystolic AP, which destroys the original propagating AP.

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