@article {23336,
	title = {Non-equilibrium reactivation of Na+ current drives early afterdepolarizations in mouse ventricle},
	journal = {Circulation: Arrhythmia and Electrophysiology},
	volume = {7},
	year = {2014},
	pages = {1205-1213},
	publisher = {Lippincott Williams \& Wilkins (United States)},
	address = {Worldwide},
	author = {Andrew G {Edwards} and Grandi, Eleonora and Johan Elon {Hake} and Patel, Sonia and Li, Pan and Miyamoto, Shigeki and Jeffrey H. {Omens} and Joan Heller {Brown} and Donald M. {Bers} and Andrew D. {McCulloch}}
}
@article {Simula.simula.2274,
	title = {Mathematical Models of Cardiac Pacemaking Function},
	journal = {Frontiers in Physics},
	volume = {1},
	number = {20},
	year = {2013},
	month = {October 2013},
	abstract = {Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This has led, for example, to more profound understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.},
	doi = {10.3389/fphy.2013.00020},
	author = {Li, Pan and Glenn T. {Lines} and Maleckar, Molly and Tveito, Aslak}
}
@article {Simula.SC.644,
	title = {On Defining Candidate Drug Characteristics for Long-QT},
	journal = {Mathematical Biosciences and Engineering},
	volume = {8},
	number = {3},
	year = {2011},
	pages = {861-873},
	abstract = {Mutations of the SCN5A gene can significantly alter the function of cardiac myocyte sodium channels leading to increased risk of ventricular arrhythmia. Several gain-of-function mutations associated with long QT intervals result in a persistent late current that prolongs the cardiac action potential. Over the past decade, Markov models of the action potential of wild type and mutant cardiac cells have been developed. The effects of drugs on mutant cells have also been incorporated into some of these models. It is the purpose of this paper to predict the effects on sodium currents and whole cell action potentials of theoretical drugs targeting the mutant sodium channel. Our aim is to compute advantageous properties of a hypothetical drug by deriving Markov model parameters of the drug action that: (a) restores the steady-state open probability of the mutant channel to that of normal wildtype channels; and (b) minimizes the difference between whole cell currents in drugged mutant and wildtype cells. The difference in the electrochemical state vector of the cell can be measured in a norm taking all components and their dynamical properties into account. Measured with this norm, the difference between the state of the mutant and wild type cell was reduced by a factor of 36 after the drug was introduced and by factors of 4 over mexitiline and 25 over lidocaine. The results suggest the potential to synthesize more effective drugs based on mechanisms of action of existing compounds.},
	author = {Tveito, Aslak and Glenn T. {Lines} and Li, Pan and Andrew D. {McCulloch}}
}
@article {Simula.sc.792,
	title = {Computational Modeling of the Initiation and Development of Spontaneous Intracellular Ca2+ Waves in Ventricular Myocytes},
	journal = {Philosophical Transactions of the Royal Society A},
	volume = {368},
	number = {1925},
	year = {2010},
	month = {August},
	pages = {3953-3965},
	doi = {10.1098/rsta.2010.0146},
	author = {Li, Pan and Wei, Wenjie and Cai, Xing and Soeller, Christian and Cannell, Mark and Arun V. {Holden}}
}
@misc {Simula.sc.840,
	title = {Antiarrhythmic Drug Identifaction},
	howpublished = {Presented at the Bidomain Workshop, Graz, Austria},
	year = {2009},
	note = {Presented at the Bidomain Workshop, Graz, Austria},
	author = {Glenn T. {Lines} and Tveito, Aslak and Li, Pan}
}
@inproceedings {Simula.SC.204,
	title = {Evolution of Intracellular Ca2+ Waves From About 10,000 RyR Clusters: Towards Solving a Computationally Daunting Task},
	journal = {The Fifth International Conference on Functional Imaging and Modeling of the Heart},
	year = {2009},
	pages = {11-20},
	publisher = {Springer},
	type = {Conference},
	doi = {10.1007/978-3-642-01932-6},
	author = {Li, Pan and Wei, Wenjie and Cai, Xing and Soeller, Christian and Cannell, Mark and Arun V. {Holden}},
	editor = {Ayache, Nicholas and Delingette, Herv{\'e} and Sermesant, Maxime}
}
@article {Simula.SC.222,
	title = {Intracellular Ca2+ Nonlinear Wave Behaviours in a Three Dimensional Ventricular Cell Model},
	journal = {Physica D: Nonlinear Phenomena},
	volume = {238},
	number = {11-12},
	year = {2009},
	pages = {992-999},
	abstract = {Intracellular Ca2+ activity regulates a wide range of cellular biochemical processes; in muscle cells, it links membrane excitation to contraction. Ca2+ dynamics includes both synchronous oscillations, and nonlinear wave phenomena, both arising from the superposition of spatially localised stochastic events, such as Ca2+ sparks. We incorporated individualised cell geometry reconstructed from confocal microscopy with realistic spatial distribution of RyR clusters into the three dimensional ventricular cell model, and reproduced complex spatio-temporal intracellular wave patterns from Ca2+ sparks. We also introduced a detailed nuclear Ca2+ handing model to simulate prolonged nuclear Ca2+ transient, and study the effects of cytosolic-nuclear coupling on intracellular Ca2+ dynamics. The model provides a computational platform to study intracellular Ca2+ with the ability to interact with experimental measurements of subcellular structures, and can be modified for other cell types.},
	doi = {10.1016/j.physd.2008.12.008},
	author = {Li, Pan and Holden, Arun}
}
@article {Simula.SC.220,
	title = {Three-Dimensional High-Resolution Imaging of Cardiac Proteins to Construct Models of Intracellular Ca2+ Signalling},
	journal = {Experimental Physiology},
	volume = {94},
	number = {5},
	year = {2009},
	month = {May},
	pages = {496-508},
	abstract = {Quantitative understanding of the Ca2+ handling in cardiac ventricular myocytes requires accurate knowledge of cardiac ultrastructure and protein distribution. We have therefore developed high-resolution imaging and analysis approaches to measure the threedimensional distribution of immuno-labelled proteins with confocal microscopy. Labelling of single rat cardiac myocytes with an antibody for the z-line marker \alpha-actinin revealed a complex architecture of sarcomere misalignment across single cells. Double immuno-labelling was used to relate the z-line structure to the distribution of ryanodine receptors (RyRs, the intracellular Ca2+ release channels), and the transverse tubular system. Both RyR and transverse tubular system distributions exhibited frequent dislocations from the simple planar geometry generally assumed in existing mathematical models. To investigate potential effects of these irregularities on Ca2+ dynamics we determined the three-dimensional distribution of RyR clusters within an extended section of a single rat ventricular myocyte to construct a model of stochastic Ca2+ dynamics with a measured Ca2+ release unit (CRU) distribution. Calculations with this model were compared to a second model in which all CRUs where placed on flat planes at a sarcomere spacing of 1.8 μm. The model with a realistic CRU distribution supported Ca2+ waves that spread axially along the cell at velocities of \~50 μm/s. By contrast, in the model with planar CRU distribution axial wave spread was slowed \~two-fold and wave propagation often nearly faltered. These results demonstrate that spatial features of the CRU distribution on multiple length scales between may significantly affect intracellular Ca2+ dynamics and must be captured in detailed mechanistic models to achieve quantitative as well as qualitative insight.},
	doi = {10.1113/expphysiol.2008.043976},
	author = {Soeller, Christian and Jayasinghe, Isuru and Li, Pan and Holden, Arun and Cannell, Mark}
}
