Faculty Opinions recommendation of Subcellular calcium dynamics in a whole-cell model of an atrial myocyte.

2012 ◽  
Author(s):  
Geneviève Dupont
Keyword(s):  
Cell Model ◽  
Calcium Dynamics ◽  
Whole Cell ◽  
Atrial Myocyte

scholarly journals Subcellular calcium dynamics in a whole-cell model of an atrial myocyte

2012 ◽  
Vol 109 (6) ◽  
pp. 2150-2155 ◽  
Author(s):  
R. Thul ◽  
S. Coombes ◽  
H. L. Roderick ◽  
M. D. Bootman
Keyword(s):  
Cell Model ◽  
Calcium Dynamics ◽  
Whole Cell ◽  
Atrial Myocyte

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.

scholarly journals Calcium homeostasis in a local/global whole cell model of permeabilized ventricular myocytes with a Langevin description of stochastic calcium release

2015 ◽  
Vol 308 (5) ◽  
pp. H510-H523 ◽  
Author(s):  
Xiao Wang ◽  
Seth H. Weinberg ◽  
Yan Hao ◽  
Eric A. Sobie ◽  
Gregory D. Smith
Keyword(s):  
Calcium Release ◽  
Ventricular Myocytes ◽  
Cell Model ◽  
Ryanodine Receptors ◽  
Planck Equation ◽  
Linear Increase ◽  
Langevin Equations ◽  
Cell Models ◽  
Whole Cell ◽  
Alternative Approach

Population density approaches to modeling local control of Ca2+-induced Ca2+ release in cardiac myocytes can be used to construct minimal whole cell models that accurately represent heterogeneous local Ca2+ signals. Unfortunately, the computational complexity of such “local/global” whole cell models scales with the number of Ca2+ release unit (CaRU) states, which is a rapidly increasing function of the number of ryanodine receptors (RyRs) per CaRU. Here we present an alternative approach based on a Langevin description of the collective gating of RyRs coupled by local Ca2+ concentration ([Ca2+]). The computational efficiency of this approach no longer depends on the number of RyRs per CaRU. When the RyR model is minimal, Langevin equations may be replaced by a single Fokker-Planck equation, yielding an extremely compact and efficient local/global whole cell model that reproduces and helps interpret recent experiments that investigate Ca2+ homeostasis in permeabilized ventricular myocytes. Our calculations show that elevated myoplasmic [Ca2+] promotes elevated network sarcoplasmic reticulum (SR) [Ca2+] via SR Ca2+-ATPase-mediated Ca2+ uptake. However, elevated myoplasmic [Ca2+] may also activate RyRs and promote stochastic SR Ca2+ release, which can in turn decrease SR [Ca2+]. Increasing myoplasmic [Ca2+] results in an exponential increase in spark-mediated release and a linear increase in nonspark-mediated release, consistent with recent experiments. The model exhibits two steady-state release fluxes for the same network SR [Ca2+] depending on whether myoplasmic [Ca2+] is low or high. In the later case, spontaneous release decreases SR [Ca2+] in a manner that maintains robust Ca2+ sparks.

scholarly journals Towards a Whole-Cell Model of Ribosome Biogenesis: Kinetic Modeling of SSU Assembly

2015 ◽  
Vol 108 (2) ◽  
pp. 390a
Author(s):  
Tyler M. Earnest ◽  
Ke Chen ◽  
Jonathan Lai ◽  
Zan Luthey-Schulten
Keyword(s):  
Kinetic Modeling ◽  
Ribosome Biogenesis ◽  
Cell Model ◽  
Whole Cell

scholarly journals Probing red blood cell mechanics, rheology and dynamics with a two-component multi-scale model

2014 ◽  
Vol 372 (2021) ◽  
pp. 20130389 ◽  
Author(s):  
Xuejin Li ◽  
Zhangli Peng ◽  
Huan Lei ◽  
Ming Dao ◽  
George Em Karniadakis
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Model ◽  
Microfluidic Channel ◽  
Scale Model ◽  
Cross Sectional ◽  
Whole Cell ◽  
Multi Scale ◽  
Rbc Membrane ◽  
Two Component

This study is partially motivated by the validation of a new two-component multi-scale cell model we developed recently that treats the lipid bilayer and the cytoskeleton as two distinct components. Here, the whole cell model is validated and compared against several available experiments that examine red blood cell (RBC) mechanics, rheology and dynamics. First, we investigated RBC deformability in a microfluidic channel with a very small cross-sectional area and quantified the mechanical properties of the RBC membrane. Second, we simulated twisting torque cytometry and compared predicted rheological properties of the RBC membrane with experimental measurements. Finally, we modelled the tank-treading (TT) motion of a RBC in a shear flow and explored the effect of channel width variation on the TT frequency. We also investigated the effects of bilayer–cytoskeletal interactions on these experiments and our simulations clearly indicated that they play key roles in the determination of cell membrane mechanical, rheological and dynamical properties. These simulations serve as validation tests and moreover reveal the capabilities and limitations of the new whole cell model.

scholarly journals Calcium Dynamics and cell model.

2003 ◽  
Vol 10 (3) ◽  
pp. 164-170
Author(s):  
TAKAAKI MICHIKAWA
Keyword(s):  
Cell Model ◽  
Calcium Dynamics

scholarly journals Modeling the role of endoplasmic reticulum-mitochondria microdomains in calcium dynamics

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Arash Moshkforoush ◽  
Baarbod Ashenagar ◽  
Nikolaos M. Tsoukias ◽  
B. Rita Alevriadou
Keyword(s):  
Endoplasmic Reticulum ◽  
Vascular Endothelial Cells ◽  
Cell Model ◽  
Vascular Endothelial ◽  
Calcium Dynamics ◽  
Mitochondrial Membranes ◽  
Excitable Cells ◽  
Closed Cell ◽  
Stimulation Of

AbstractUpon inositol trisphosphate (IP3) stimulation of non-excitable cells, including vascular endothelial cells, calcium (Ca2+) shuttling between the endoplasmic reticulum (ER) and mitochondria, facilitated by complexes called Mitochondria-Associated ER Membranes (MAMs), is known to play an important role in the occurrence of cytosolic Ca2+ concentration ([Ca2+]Cyt) oscillations. A mathematical compartmental closed-cell model of Ca2+ dynamics was developed that accounts for ER-mitochondria Ca2+ microdomains as the µd compartment (besides the cytosol, ER and mitochondria), Ca2+ influx to/efflux from each compartment and Ca2+ buffering. Varying the distribution of functional receptors in MAMs vs. the rest of ER/mitochondrial membranes, a parameter called the channel connectivity coefficient (to the µd), allowed for generation of [Ca2+]Cytoscillations driven by distinct mechanisms at various levels of IP3 stimulation. Oscillations could be initiated by the transient opening of IP3 receptors facing either the cytosol or the µd, and subsequent refilling of the respective compartment by Ca2+ efflux from the ER and/or the mitochondria. Only under conditions where the µd became the oscillation-driving compartment, silencing the Mitochondrial Ca2+ Uniporter led to oscillation inhibition. Thus, the model predicts that alternative mechanisms can yield [Ca2+]Cyt oscillations in non-excitable cells, and, under certain conditions, the ER-mitochondria µd can play a regulatory role.

cAMP-activated anion conductance is associated with expression of CFTR in neonatal mouse cardiac myocytes

2000 ◽  
Vol 278 (2) ◽  
pp. C436-C450 ◽  
Author(s):  
Alan S. Lader ◽  
Yihan Wang ◽  
G. Robert Jackson ◽  
Steven C. Borkan ◽  
Horacio F. Cantiello
Keyword(s):  
Monoclonal Antibody ◽  
Cardiac Myocytes ◽  
Single Channel ◽  
Cell Model ◽  
Neonatal Mouse ◽  
Intracellular Camp ◽  
Mouse Heart ◽  
Whole Cell ◽  
Anion Conductance ◽  
Camp Stimulation

In this study, patch-clamp techniques were applied to cultured neonatal mouse cardiac myocytes (NMCM) to assess the contribution of cAMP stimulation to the anion permeability in this cell model. Addition of either isoproterenol or a cocktail to raise intracellular cAMP increased the whole cell currents of NMCM. The cAMP-dependent conductance was largely anionic, as determined under asymmetrical (low intracellular) Cl− conditions and symmetrical Cl−in the presence of various counterions, including Na+, Mg2+, Cs+, and N-methyl-d-glucamine. Furthermore, the cAMP-stimulated conductance was also permeable to ATP. The cAMP-activated currents were inhibited by diphenylamine-2-carboxylate, glibenclamide, and an anti-cystic fibrosis transmembrane conductance regulator (CFTR) monoclonal antibody. The anti-CFTR monoclonal antibody failed, however, to inhibit an osmotically activated anion conductance, indicating that CFTR is not linked to osmotically stimulated currents in this cell model. Immunodetection studies of both neonatal mouse heart tissue and cultured NMCM revealed that CFTR is expressed in these preparations. The implication of CFTR in the cAMP-stimulated Cl−- and ATP-permeable conductance was further verified with NMCM of CFTR knockout mice [ cftr(−/−)] in which cAMP stimulation was without effect on the whole cell currents. In addition, stimulation with protein kinase A and ATP induced Cl−-permeable single-channel activity in excised, inside-out patches from control, but not cftr(−/−) NMCM. The data in this report indicate that cAMP stimulation of NMCM activates an anion-permeable conductance with functional properties similar to those expected for CFTR, thus suggesting that CFTR may be responsible for the cAMP-activated conductance. CFTR may thus contribute to the permeation and/or regulation of Cl−- and ATP-permeable pathways in the developing heart.

Abstract 19749: Cardiac-specific Deletion of Caveolin-3 Delays Repolarization and Increases Susceptibility to Ventricular Arrhythmia

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yogananda S Markandeya ◽  
Li Feng ◽  
Vignesh Ramchandran ◽  
Ravi Vaidyanathan ◽  
Jabe Best ◽  
...  
Keyword(s):  
Contractile Function ◽  
Cell Model ◽  
Histopathological Examination ◽  
Scaffolding Protein ◽  
Macromolecular Complex ◽  
Cardiac Structure ◽  
Qtc Interval ◽  
Long Qt ◽  
Whole Cell ◽  
Significant Difference

Caveolin-3 (Cav-3) is an essential scaffolding protein for formation of caveolae in muscle cells. Cav-3 is part of a macromolecular complex including several ion channels. Mutations in Cav-3 have been associated with the inherited long QT syndrome as well as a variety of skeletal myopathies. To investigate the role of Cav-3 in heart and whether loss of function of Cav-3 explains the long QT phenotype, we generated cardiac-specific, inducible Cre-lox Cav-3 knockout mice. 8 week old mice were treated with tamoxifen in the chow to induce cardiac-specific recombination. Western blot analysis and transmitted electron microscopy demonstrated a graded loss of Cav-3 and caveolae in Cav-3 KO heterozygous mice (Cav-3-/+), Cav-3 KO homozygous mice (Cav-3-/-) relative to the littermate controls mice (WT). Echocardiography revealed no significant difference in %EF, %FS, LV chamber dimensions, and LV wall thickness between the different genotypes. Histopathological examination demonstrated no significant difference in HW/BW ratio, cardiac structure or fibrosis comparing Cav-3-/- and WT mice. Telemetry ECG recordings revealed a significant increase in QTc interval Cav-3-/- (68.5±7 ms) compared to WT (54.83±6 ms). Whole cell patch clamp analysis from isolated ventricular myocytes indicated a progressive increase in action potential duration (APD) with loss of Cav-3: WT (APD50: 4.7 ± 1ms; APD90: 28.0±3 ms; n=9); Cav-3-/+(APD50: 10.3±2 ms; APD90: 42.4±3 ms; n=13), Cav-3-/- (APD50: 32.4±6ms; APD90: 97.4±7ms; n=12). Whole cell voltage clamp measurements from Cav-3-/- revealed increased late INa, decrease in ICa,L, Ito,Iss current density without altering peak INa compared to WT cells, and these current changes were adequate to explain the increased APD based on computational representation using the Morotti et al. mouse ventricular cell model. Intracardiac programmed electrical stimulation (ventricular burst pacing) induced VT/Vfib in 8 out of 9 Cav3-/- but none of WT mice (0/5). Our results demonstrate that loss of Cav-3 and caveolae in adult mice does not alter cardiac structure or contractile function but leads to prolonged APD, an increased in QTc, and increased susceptibility to ventricular arrhythmias.

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