scholarly journals Excitation-Contraction Coupling between Human Atrial Myocytes with Fibroblasts and Stretch Activated Channel Current: A Simulation Study

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Heqing Zhan ◽  
Ling Xia
Keyword(s):  
Simulation Study ◽  
Mechanical Model ◽  
Tissue Level ◽  
Resting Membrane Potential ◽  
Cardiac Modeling ◽  
Electrical Excitation ◽  
Channel Current ◽  
Modeling Studies ◽  
Atrial Myocyte ◽  
Human Atrial Myocyte

Myocytes have been regarded as the main objectives in most cardiac modeling studies and attracted a lot of attention. Connective tissue cells, such as fibroblasts (Fbs), also play crucial role in cardiac function. This study proposed an integrated myocyte-Isac-Fb electromechanical model to investigate the effect of Fbs and stretch activated ion channel current (Isac) on cardiac electrical excitation conduction and mechanical contraction. At the cellular level, an active Fb model was coupled with a human atrial myocyte electrophysiological model (includingIsac) and a mechanical model. At the tissue level, electrical excitation conduction was coupled with an elastic mechanical model, in which finite difference method (FDM) was used to solve the electrical excitation equations, while finite element method (FEM) was used for the mechanics equations. The simulation results showed that Fbs andIsaccoupling caused diverse effects on action potential morphology during repolarization, depolarized the resting membrane potential of the human atrial myocyte, slowed down wave propagation, and decreased strains in fibrotic tissue. This preliminary simulation study indicates that Fbs andIsachave important implications for modulating cardiac electromechanical behavior and should be considered in future cardiac modeling studies.

scholarly journals Effects of Na+Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Heqing Zhan ◽  
Jingtao Zhang ◽  
Jialun Lin ◽  
Guilai Han
Keyword(s):  
Mathematical Modeling ◽  
Membrane Potential ◽  
Action Potential ◽  
Channel Current ◽  
Voltage Gated Sodium Channels ◽  
Atrial Myocyte ◽  
Experimental Findings ◽  
Human Atrial Myocyte ◽  
Coupling Conductance ◽  
Basic Cycle Length

Fibrotic remodeling, characterized by fibroblast phenotype switching, is often associated with atrial fibrillation and heart failure. This study aimed to investigate the effects on electrotonic myofibroblast-myocyte (Mfb-M) coupling on cardiac myocytes excitability and repolarization of the voltage-gated sodium channels (VGSCs) and single mechanogated channels (MGCs) in human atrial Mfbs. Mathematical modeling was developed from a combination of (1) models of the human atrial myocyte (including the stretch activated ion channel current,ISAC) and Mfb and (2) our formulation of currents through VGSCs (INa_Mfb) and MGCs (IMGC_Mfb) based upon experimental findings. The effects of changes in the intercellular coupling conductance, the number of coupled Mfbs, and the basic cycle length on the myocyte action potential were simulated. The results demonstrated that the integration ofISAC,INa_Mfb, andIMGC_Mfbreduced the amplitude of the myocyte membrane potential(Vmax)and the action potential duration (APD), increased the depolarization of the resting myocyte membrane potential(Vrest), and made it easy to trigger spontaneous excitement in myocytes. For Mfbs, significant electrotonic depolarizations were exhibited with the addition ofINa_MfbandIMGC_Mfb. Our results indicated thatISAC,INa_Mfb, andIMGC_Mfbsignificantly influenced myocytes and Mfbs properties and should be considered in future cardiac pathological mathematical modeling.

scholarly journals Accelerating mono-domain cardiac electrophysiology simulations using OpenCL

2015 ◽  
Vol 1 (1) ◽  
pp. 413-417
Author(s):  
Eike M. Wülfers ◽  
Zhasur Zhamoliddinov ◽  
Olaf Dössel ◽  
Gunnar Seemann
Keyword(s):  
Cardiac Electrophysiology ◽  
Cardiac Tissue ◽  
Ionic Currents ◽  
Domain Model ◽  
Electrical Excitation ◽  
Simulation Domain ◽  
Speed Up ◽  
Cross Platform ◽  
Atrial Myocyte ◽  
Intel Xeon

AbstractUsing OpenCL, we developed a cross-platform software to compute electrical excitation conduction in cardiac tissue. OpenCL allowed the software to run parallelized and on different computing devices (e.g., CPUs and GPUs). We used the macroscopic mono-domain model for excitation conduction and an atrial myocyte model by Courtemanche et al. for ionic currents. On a CPU with 12 HyperThreading-enabled Intel Xeon 2.7 GHz cores, we achieved a speed-up of simulations by a factor of 1.6 against existing software that uses OpenMPI. On two high-end AMD FirePro D700 GPUs the OpenCL software ran 2.4 times faster than the OpenMPI implementation. The more nodes the discretized simulation domain contained, the higher speed-ups were achieved.

scholarly journals An individual-based mechanical model of cell movement in heterogeneous tissues and its coarse-grained approximation

2018 ◽  
Author(s):  
R. J. Murphy ◽  
P. R. Buenzli ◽  
R. E. Baker ◽  
M. J. Simpson
Keyword(s):  
Mechanical Model ◽  
Numerical Solutions ◽  
Cell Movement ◽  
Biological Tissues ◽  
Tissue Level ◽  
Cellular Level ◽  
Coarse Grained ◽  
Mechanical Heterogeneity ◽  
Single Scale ◽  
The Individual

AbstractMechanical heterogeneity in biological tissues, in particular stiffness, can be used to distinguish between healthy and diseased states. However, it is often difficult to explore relationships between cellular-level properties and tissue-level outcomes when biological experiments are performed at a single scale only. To overcome this difficulty we develop a multi-scale mathematical model which provides a clear framework to explore these connections across biological scales. Starting with an individual-based mechanical model of cell movement, we subsequently derive a novel coarse-grained system of partial differential equations governing the evolution of the cell density due to heterogeneous cellular properties. We demonstrate that solutions of the individual-based model converge to numerical solutions of the coarse-grained model, for both slowly-varying-in-space and rapidly-varying-in-space cellular properties. Applications of the model are discussed, including determining relative cellular-level properties and an interpretation of data from a breast cancer detection experiment.

scholarly journals Effects of Ultrastructural Remodeling on Calcium Signaling and Electrophysiology in a Three-Dimensional Model of the Human Atrial Myocyte

2020 ◽  
Vol 118 (3) ◽  
pp. 256a
Author(s):  
Xianwei Zhang ◽  
Haibo Ni ◽  
Stefano Morotti ◽  
William E. Louch ◽  
Andrew G. Edwards ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Three Dimensional ◽  
Dimensional Model ◽  
Three Dimensional Model ◽  
Atrial Myocyte ◽  
Human Atrial Myocyte

ONSET AND TERMINATION OF REENTRANT EXCITATION IN HOMOGENEOUS HUMAN VIRTUAL ATRIAL TISSUE

2003 ◽  
Vol 13 (12) ◽  
pp. 3631-3643 ◽  
Author(s):  
H. ZHANG ◽  
C. J. GARRAT ◽  
A. V. HOLDEN
Keyword(s):  
Electrical Stimulus ◽  
Parabolic Partial Differential Equation ◽  
Atrial Arrhythmias ◽  
Excitation Wave ◽  
Cellular Models ◽  
Rate Dependent ◽  
Dynamical Behaviors ◽  
Atrial Myocyte ◽  
Reentrant Excitation ◽  
Human Atrial Myocyte

Multicellular models of homogeneous and isotropic human atria have been developed by incorporating cellular models of membrane electrical activity of single human atrial myocyte into a parabolic partial differential equation. These models are used to study the rate dependent conduction velocity of excitation wave, vulnerability of tissue to reentry and dynamical behaviors of reentry. Bidomain models were also developed to study the actions of a large and brief external electrical stimulus on wave propagation in human atria. These studies provide basic insights to understand the onset and termination of atrial arrhythmias in the human heart.

scholarly journals K+current changes account for the rate dependence of the action potential in the human atrial myocyte

2009 ◽  
Vol 297 (4) ◽  
pp. H1398-H1410 ◽  
Author(s):  
Mary M. Maleckar ◽  
Joseph L. Greenstein ◽  
Wayne R. Giles ◽  
Natalia A. Trayanova
Keyword(s):  
Action Potential ◽  
Membrane Dynamics ◽  
Rate Dependence ◽  
Accurate Representation ◽  
New Model ◽  
Charge Conservation ◽  
Repolarization Reserve ◽  
Atrial Myocyte ◽  
Kinetics Of ◽  
Human Atrial Myocyte

Ongoing investigation of the electrophysiology and pathophysiology of the human atria requires an accurate representation of the membrane dynamics of the human atrial myocyte. However, existing models of the human atrial myocyte action potential do not accurately reproduce experimental observations with respect to the kinetics of key repolarizing currents or rate dependence of the action potential and fail to properly enforce charge conservation, an essential characteristic in any model of the cardiac membrane. In addition, recent advances in experimental methods have resulted in new data regarding the kinetics of repolarizing currents in the human atria. The goal of this study was to develop a new model of the human atrial action potential, based on the Nygren et al. model of the human atrial myocyte and newly available experimental data, that ensures an accurate representation of repolarization processes and reproduction of action potential rate dependence and enforces charge conservation. Specifically, the transient outward K+current ( It) and ultrarapid rectifier K+current ( IKur) were newly formulated. The inwardly recitifying K+current ( IK1) was also reanalyzed and implemented appropriately. Simulations of the human atrial myocyte action potential with this new model demonstrated that early repolarization is dependent on the relative conductances of Itand IKur, whereas densities of both IKurand IK1underlie later repolarization. In addition, this model reproduces experimental measurements of rate dependence of It, IKur, and action potential duration. This new model constitutes an improved representation of excitability and repolarization reserve in the human atrial myocyte and, therefore, provides a useful computational tool for future studies involving the human atrium in both health and disease.

ANF (99???126) and its Propeptide, ANF (1???16) are Secreted Simultaneously from the Human Atrial Myocyte

1987 ◽  
Vol 5 (5) ◽  
pp. 533-536 ◽  
Author(s):  
George B.M. Lindop ◽  
Elizabeth A. Mallon ◽  
Jane Hair ◽  
Thomas T. Downie ◽  
Gordon Maclntyre
Keyword(s):  
Atrial Myocyte ◽  
Human Atrial Myocyte

Chronic High-Inspired CO2 Decreases Excitability of Mouse Hippocampal Neurons

2007 ◽  
Vol 97 (2) ◽  
pp. 1833-1838 ◽  
Author(s):  
Xiang Q. Gu ◽  
Amjad Kanaan ◽  
Hang Yao ◽  
Gabriel G. Haddad
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Channel Current ◽  
Conductance Curve ◽  
Recovery From Inactivation ◽  
Channel Expression ◽  
Steady State Inactivation ◽  
And Function

To examine the effect of chronically elevated CO2 on excitability and function of neurons, we exposed mice to 8 and 12% CO2 for 4 wk (starting at 2 days of age), and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Chronic CO2-treated neurons (CC) had a similar input resistance ( Rm) and resting membrane potential ( Vm) as control (CON). Although treatment with 8% CO2 did not change the rheobase (64 ± 11 pA, n = 9 vs. 47 ± 12 pA, n = 8 for CC 8% vs. CON; means ± SE), 12% CO2 treatment increased it significantly (73 ± 8 pA, n = 9, P = 0.05). Furthermore, the 12% CO2 but not the 8% CO2 treatment decreased the Na+ channel current density (244 ± 36 pA/pF, n = 17, vs. 436 ± 56 pA/pF, n = 18, for CC vs. CON, P = 0.005). Recovery from inactivation was also lowered by 12% but not 8% CO2. Other gating properties of Na+ current, such as voltage-conductance curve, steady-state inactivation, and time constant for deactivation, were not modified by either treatment. Western blot analysis showed that the expression of Na+ channel types I–III was not changed by 8% CO2 treatment, but their expression was significantly decreased by 20–30% ( P = 0.03) by the 12% treatment. We conclude from these data and others that neuronal excitability and Na+ channel expression depend on the duration and level of CO2 exposure and maturational changes occur in early life regarding neuronal responsiveness to CO2.

scholarly journals Mechanisms of atrial-selective block of Na+ channels by ranolazine: I. Experimental analysis of the use-dependent block

2011 ◽  
Vol 301 (4) ◽  
pp. H1606-H1614 ◽  
Author(s):  
Andrew C. Zygmunt ◽  
Vladislav V. Nesterenko ◽  
Sridharan Rajamani ◽  
Dan Hu ◽  
Hector Barajas-Martinez ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Selective Inhibition ◽  
Resting Membrane Potential ◽  
Inactivation Curve ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
Channel Current ◽  
Ventricular Cells ◽  
293 Cells ◽  
Steady State Inactivation

Atrial-selective inhibition of cardiac Na+ channel current ( INa) and INa-dependent parameters has been shown to contribute to the safe and effective management of atrial fibrillation. The present study examined the basis for the atrial-selective actions of ranolazine. Whole cell INa was recorded at 15°C in canine atrial and ventricular myocytes and in human embryonic kidney (HEK)-293 cells expressing SCN5A. Tonic block was negligible at holding potentials from −140 to −100 mV, suggesting minimal drug interactions with the closed state. Trains of 40 pulses were elicited over a range of holding potentials to determine use-dependent block. Guarded receptor formalism was used to analyze the development of block during pulse trains. Use-dependent block by ranolazine increased at more depolarized holding potentials, consistent with an interaction of the drug with either preopen or inactivated states, but was unaffected by longer pulse durations between 5 and 200 ms, suggesting a weak interaction with the inactivated state. Block was significantly increased at shorter diastolic intervals between 20 and 200 ms. Responses in atrial and ventricular myocytes and in HEK-293 cells displayed a similar pattern. Ranolazine is an open state blocker that unbinds from closed Na+ channels unusually fast but is trapped in the inactivated state. Kinetic rates of ranolazine interactions with different states of atrial and ventricular Na+ channels were similar. Our data suggest that the atrial selectivity of ranolazine is due to a more negative steady-state inactivation curve, less negative resting membrane potential, and shorter diastolic intervals in atrial cells compared with ventricular cells at rapid rates.

Sign in / Sign up

Export Citation Format

Share Document