Spontaneous Calcium Release in Cardiac Myocytes: Store Overload and Electrical Dynamics

Alexander, Amanda F.; DeNardo, Erin Kathleen; Frazier, Eric; McCauley, Michael; Rojina, Nicholas; Coulibaly, Zana; Peercy, Bradford E.; Izu, Leighton T.

doi:10.30707/spora1.1alexander

Cited by 6 publications

(29 citation statements)

References 26 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the concentration of calcium in the cytosol begins to change, this causes depolarizations of the cell plasma membrane, which, in turn, causes the action potential that leads to the opening of the L-type Calcium Channels (LCC). This process of action potential causes the LCC to open which is the feedforward mechanism represented as link 1 ○ in Figure 1.1. This feedforward mechanism allows for the electrical excitation to influence the calcium concentration in the cytosol.…”

Section: Dynamics Of a Cardiac Cellmentioning

confidence: 99%

“…This feedforward mechanism allows for the electrical excitation to influence the calcium concentration in the cytosol. The previously mentioned methods, represented by links 1 ○ and 2 ○, lead to a two-way connection between the electrical excitation and calcium signaling occuring in the cardiac cell.…”

Section: Dynamics Of a Cardiac Cellmentioning

confidence: 99%

“…This original model comprises the heart of the Calcium Signaling component of the system indicated in Figure 1.1. The model was extended for the first time to include the Electrical Excitation component in Figure 1.1 in [1], which implemented a one-way interaction from electrical excitation to calcium signaling indicated by link 1 ○ in Figure 1.1. Studies with six variables in [2] extended the coupling to include a two-way cycle between electrical excitation and calcium signaling by incorporating both links 1 ○ and 2 ○ in Figure 1.1.…”

Section: Introductionmentioning

confidence: 99%

“…The model was extended for the first time to include the Electrical Excitation component in Figure 1.1 in [1], which implemented a one-way interaction from electrical excitation to calcium signaling indicated by link 1 ○ in Figure 1.1. Studies with six variables in [2] extended the coupling to include a two-way cycle between electrical excitation and calcium signaling by incorporating both links 1 ○ and 2 ○ in Figure 1.1. The 2016 paper [2] also introduced the formulation of the complete eight-variable model for all components in Figure 1.1, but not all model variables were used in the simulations, and the studies did not incorporate the mechanical system.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, this work uses a model with seven variables to represent the excitationcontraction coupling (ECC) occurring in the cardiomyocyte, in which CICR is the mechanism through which electrical excitation is coupled with mechanical contraction through calcium signaling. The three components of the model and their links labeled 1 ○ to 4 ○.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Examining the Electrical Excitation, Calcium Signaling, and Mechanical Contraction Cycle in a Heart Cell

Deetz¹,

Foster²,

Leftwich³

et al. 2017

SPORA

Self Cite

View full text Add to dashboard Cite

As the leading cause of death in the United States, heart disease has become a principal concern in modern society. Cardiac arrhythmias can be caused by a dysregulation of calcium dynamics in cardiomyocytes. Calcium dysregulation, however, is not yet fully understood and is not easily predicted; this provides motivation for the subsequent research. Excitationcontraction coupling (ECC) is the process through which cardiomyocytes undergo contraction from an action potential. Calcium induced calcium release (CICR) is the mechanism through which electrical excitation is coupled with mechanical contraction through calcium signaling. The study of the interplay between electrical excitation, calcium signaling, and mechanical contraction has the potential to improve our understanding of the regular functioning of the cardiomyocytes and help us understand how any dysregulation can lead to potential cardiac arrhythmias. ECC, of which CICR is an important part, can be modeled using a system of partial differential equations that link the electrical excitation, calcium signaling, and mechanical contraction components of a cardiomyocyte. We extend a previous model [Angeloff et al., Spora, 2016] to implement a seven-variable model that includes for the first time the mechanical component of the ECC. We study how the interaction of electrical and calcium systems can impact the cardiomyocyte's levels of contraction.

show abstract

Section: Dynamics Of a Cardiac Cellmentioning

confidence: 99%

Section: Dynamics Of a Cardiac Cellmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Examining the Electrical Excitation, Calcium Signaling, and Mechanical Contraction Cycle in a Heart Cell

Deetz¹,

Foster²,

Leftwich³

et al. 2017

SPORA

Self Cite

View full text Add to dashboard Cite

show abstract

Challenges and opportunities for the simulation of calcium waves on modern multi‐core and many‐core parallel computing platforms

Barajas

Gobbert

Kroiz

et al. 2019

Numer Methods Biomed Eng

Self Cite

View full text Add to dashboard Cite

State-of-the-art distributed-memory computer clusters contain multi-core CPUs with 16 and more cores. The second-generation of the Intel Xeon Phi many-core processor has more than 60 cores with 16 GB of high-performance on-chip memory. We contrast the performance of the second-generation Intel Xeon Phi, code-named Knights Landing (KNL), with 68 computational cores to the latest multi-core CPU Intel Skylake with 18 cores. A special-purpose code solving a system of nonlinear reaction-diffusion partial differential equations with several thousands of point sources modeled mathematically by Dirac delta distributions serves as realistic test bed. The system is discretized in space by the finite volume method and advanced by fully implicit time-stepping, with a matrix-free implementation that allows the complex model to have an extremely small memory footprint. The sample application is a seven variable model of calcium induced calcium release (CICR) that models the interplay between electrical excitation, calcium signaling, and mechanical contraction in a heart cell. The results demonstrate that excellent parallel scalability is possible on both hardware platforms, but that modern multi-core CPUs outperform the specialized many-core Intel Xeon Phi KNL architecture for a large class of problems such as systems of parabolic partial differential equations.

show abstract

Long-time simulations with complex code using multiple nodes of Intel Xeon Phi Knights Landing

Graf

Gobbert

Khuvis

2018

Journal of Computational and Applied Mathematics

View full text Add to dashboard Cite

Modern partial differential equation (PDE) models across scientific disciplines require sophisticated numerical methods resulting in complex codes as well as large numbers of simulations for analysis like parameter studies and uncertainty quantification. To evaluate the behavior of the model for sufficeintly long times, for instance, to compare to laboratory time scales, often requires long-time simulations with small time steps and high mesh resolutions. This motivates the need for very efficient numerical methods and the use of parallel computing on the most recent modern architectures. We use complex code resulting from a PDE model of calcium dynamics in a heart cell to analyze the performance of the recently released Intel Xeon Phi Knights Landing (KNL). The KNL is a second-generation many-integrated-core (MIC) processor released in 2016 with a theoretical peak performance of over 3 TFLOP/s of double-precision floating-point operations for which complex codes can be easily ported because of the x86 compatibility of each KNL core. We demonstrate the benefit of hybrid MPI+OpenMP code when implemented effectively and run efficiently on the KNL including on multiple KNL nodes. For multi-KNL runs for our sample code, it is shown to be optimal to use all cores of each KNL, one MPI process on every other tile, and only two of the maximum of four threads per core.

show abstract

Spontaneous Calcium Release in Cardiac Myocytes: Store Overload and Electrical Dynamics

Cited by 6 publications

References 26 publications

Examining the Electrical Excitation, Calcium Signaling, and Mechanical Contraction Cycle in a Heart Cell

Examining the Electrical Excitation, Calcium Signaling, and Mechanical Contraction Cycle in a Heart Cell

Challenges and opportunities for the simulation of calcium waves on modern multi‐core and many‐core parallel computing platforms

Long-time simulations with complex code using multiple nodes of Intel Xeon Phi Knights Landing

Contact Info

Product

Resources

About