A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

Mahajan, A.; Shiferaw, Y.; Sato, D.; Baher, A.; Olcese, R.; Xie, L.-H.; Yang, M.-J.; Chen, P.-S.; Restrepo, Juan G.; Grafinkel, A.; Qu, Z.; Weiss, James N.

doi:10.1529/biophysj.106.098160

Cited by 48 publications

(98 citation statements)

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“…We carried out simulations to examine the threshold for TA in the rabbit ventricular myocyte model by Mahajan et al (20). The spontaneous Ca 2þ release that causes a DAD or TA was simulated by a clamped Ca 2þ transient (see Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

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A Dynamical Threshold for Cardiac Delayed Afterdepolarization-Mediated Triggered Activity

Liu

Song

et al. 2016

Biophysical Journal

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Ventricular myocytes are excitable cells whose voltage threshold for action potential (AP) excitation is~À60 mV at which I Na is activated to give rise to a fast upstroke. Therefore, for a short stimulus pulse to elicit an AP, a stronger stimulus is needed if the resting potential lies further away from the I Na threshold, such as in hypokalemia. However, for an AP elicited by a long duration stimulus or a diastolic spontaneous calcium release, we observed that the stimulus needed was lower in hypokalemia than in normokalemia in both computer simulations and experiments of rabbit ventricular myocytes. This observation provides insight into why hypokalemia promotes calcium-mediated triggered activity, despite the resting potential lying further away from the I Na threshold. To understand the underlying mechanisms, we performed bifurcation analyses and demonstrated that there is a dynamical threshold, resulting from a saddle-node bifurcation mainly determined by I K1 and I NCX . This threshold is close to the voltage at which I K1 is maximum, and lower than the I Na threshold. After exceeding this dynamical threshold, the membrane voltage will automatically depolarize above the I Na threshold due to the large negative slope of the I K1 -V curve. This dynamical threshold becomes much lower in hypokalemia, especially with respect to calcium, as predicted by our theory. Because of the saddle-node bifurcation, the system can automatically depolarize even in the absence of I Na to voltages higher than the I Ca,L threshold, allowing for triggered APs in single myocytes with complete I Na block. However, because I Na is important for AP propagation in tissue, blocking I Na can still suppress premature ventricular excitations in cardiac tissue caused by calcium-mediated triggered activity. This suppression is more effective in normokalemia than in hypokalemia due to the difference in dynamical thresholds.

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Section: Resultsmentioning

confidence: 99%

“…Computer simulations were performed in a single cell and one-dimensional (1D) cables using the AP model previously described by Mahajan et al (20). In the single-cell simulations, the cell model was first prepaced to its steady state.…”

Section: Computer Simulationsmentioning

confidence: 99%

A Dynamical Threshold for Cardiac Delayed Afterdepolarization-Mediated Triggered Activity

Liu

Song

et al. 2016

Biophysical Journal

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“…Cardiac electrophysiology models often do not include tension development, but given that peak tension is reached during the decay phase of the calcium transient and that calcium buffering will have the greatest effect during peak calcium, the static unbinding rate of calcium could be approximated as ~100s -1 . This is not easily compatible with the routinely used values of 19.6s -1 (Bondarenko et al 2004, Mahajan et al 2008, Shannon et al 2000, 40s -1 (Iyer et al 2004, Pandit et al 2001) and 200s -1 (Noble et al 1998). …”

Section: Models Of Cell Contractionmentioning

confidence: 85%

“…Along with human ventricular models, which are discussed in detail below, ventricular models have been developed for guinea pig (Luo and Rudy 1991, Nordin 1993, Luo and Rudy 1994, Noble et al 1998, Faber and Rudy 2000, canine , Fox et al 2002, Greenstein and Winslow 2002, Cabo and Boyden 2003, Hund and Rudy 2004, Flaim et al 2006, rabbit (Puglisi and Bers 2001, Shannon et al 2004, Mahajan et al 2008, rat (Pandit et al 2001), and mouse (Bondarenko et al 2004, Wang andSobie 2008). The existence of species-specific ventricular models is a significant improvement over earlier, more generic ventricular models and recognises the differences in current contributions across species.…”

Section: Overview Of Mammalian Electrophysiology Modelsmentioning

confidence: 99%

“…From the simplest approach representing only cytosolic and SR compartments (Fox et al 2002), the transition to the most complex model with cytosolic, junctional, subsarcolemmal, NSR, JSR and troponin compartments (Mahajan et al 2008) is not obvious, since a number of "intermediate" approaches exist. Table 1 highlights this variety further, where we group models according to the number of compartments represented.…”

Section: Models Of Calcium Signalling In Cardiac Cellsmentioning

confidence: 99%

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Cardiac cell modelling: Observations from the heart of the cardiac physiome project

Fink

Niederer

Cherry

et al. 2011

Progress in Biophysics and Molecular Biology

149

136

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In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field.

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Modeling the dispersion in electromechanically coupled myocardium

Eriksson

Prassl

Plank

et al. 2013

Numer Methods Biomed Eng

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We present an approach to model the dispersion of fiber and sheet orientations in the myocardium. By utilizing structure parameters, an existing orthotropic and invariant-based constitutive model developed to describe the passive behavior of the myocardium is augmented. Two dispersion parameters are fitted to experimentally observed angular dispersion data of the myocardial tissue. Computations are performed on a unit myocardium tissue cube and on a slice of the left ventricle indicating that the dispersion parameter has an effect on the myocardial deformation and stress development. The use of fiber dispersions relating to a pathological myocardium had a rather big effect. The final example represents an ellipsoidal model of the left ventricle indicating the influence of fiber and sheet dispersions upon contraction over a cardiac cycle. Although only a minor shift in the pressure-volume (PV) loops between the cases with no dispersions and with fiber and sheet dispersions for a healthy myocardium was observed, a remarkably different behavior is obtained with a fiber dispersion relating to a diseased myocardium. In future simulations, this dispersion model for myocardial tissue may advantageously be used together with models of, for example, growth and remodeling of various cardiac diseases.

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A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

Cited by 48 publications

References 0 publications

A Dynamical Threshold for Cardiac Delayed Afterdepolarization-Mediated Triggered Activity

A Dynamical Threshold for Cardiac Delayed Afterdepolarization-Mediated Triggered Activity

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

Modeling the dispersion in electromechanically coupled myocardium

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