@article {25026,
	title = {Refractoriness in human atria: Time and voltage dependence of sodium channel availability},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {101},
	year = {2016},
	month = {12/2016},
	pages = {26-34},
	publisher = {Elsevier},
	doi = {10.1016/j.yjmcc.2016.10.009},
	url = {https://doi.org/10.1016/j.yjmcc.2016.10.009},
	author = {Skibsbye, Lasse and Jespersen, Thomas and Maleckar, Molly and van den Brink, Jonas and Tavi, Pasi and Koivum{\"a}ki, Jussi}
}
@article {Simula.simula.3028,
	title = {Calcium Signaling in Developing Cardiomyocytes: Implications for Model Systems and Disease},
	journal = {The Journal of Physiology},
	volume = {593},
	year = {2015},
	month = {03/2015},
	pages = {1047-1063},
	publisher = {John Wiley and Sons},
	abstract = {Adult cardiomyocytes exhibit complex Ca2+ homeostasis, enabling tight control of contraction and relaxation. This intricate regulatory system develops gradually, with progressive maturation of specialized structures and increasing capacity of Ca2+ sources and sinks. In this review, we outline current understanding of these developmental processes, and draw parallels to pathophysiological conditions where cardiomyocytes exhibit a striking regression to an immature state of Ca2+ homeostasis. We further highlight the importance of understanding developmental physiology when employing immature cardiomyocyte models such as neonatal cell culture and stem cells.},
	doi = {10.1113/jphysiol.2014.274712},
	url = {http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.274712/abstract},
	author = {William E. {Louch} and Koivum{\"a}ki, Jussi and Tavi, Pasi}
}
@article {Simula.simula.2200,
	title = {In Silico Screening of the Key Cellular Remodeling Targets in Chronic Atrial Fibrillation},
	journal = {PLoS Computational Biology},
	volume = {10(5)},
	number = {e1003620},
	year = {2014},
	month = {May},
	publisher = { },
	abstract = {Background - Chronic atrial fibrillation (AF) is a complex disease, with underlying changes in electrophysiology, calcium signaling and the structure of atrial myocytes. How these individual remodeling targets and their emergent interactions contribute to cell physiology in chronic AF is not well understood. Methodology/Principal Findings - In silico experiments were performed in a computational model of the human atrial myocyte. Remodeled function of cellular components was based on a broad review of the literature of in vitro findings in chronic AF, and these were integrated into the model to define a cohort of virtual cells. Simulation results indicate that while the altered function of calcium and potassium ion channels alone causes a pronounced decrease in action potential duration, remodeling of calcium handling has a substantial impact on the chronic AF phenotype as well. We also found that the reduction of intracellular calcium transient amplitude in chronic AF in comparison to normal sinus rhythm is mostly due to remodeling of calcium channel function, calcium handling and cellular geometry. Finally, we found that decreased electrical resistance of the membrane together with remodeled calcium handling synergistically decrease cellular excitability and inducibility of repolarization abnormalities in the human atrial myocyte in chronic AF. Conclusions/Significance - The results highlight the complexity of both intrinsic cellular interactions and emergent properties of human atrial myocytes in chronic AF. Therefore, reversing the remodeling for a single remodeled component does very little to restore the normal sinus rhythm phenotype. These findings may have important implications for developing novel therapeutic approaches for chronic AF.},
	author = {Koivum{\"a}ki, Jussi and Seemann, Gunnar and Maleckar, Molly and Tavi, Pasi}
}
@misc {Simula.simula.2202,
	title = {Mechanisms Promoting Chronic Atrial Fibrillation: Role of Remodelled Intracellular Calcium Handling and Cellular Hypertrophy},
	year = {2013},
	month = {February},
	abstract = {Aims: Emerging evidence suggests an important role for abnormal intracellular calcium handling in the pathophysiology of atrial fibrillation (AF). However, it is unclear how the remodeling of these ionic mechanisms, in comparison to electrical and structural remodeling, contributes to the AF substrate. Here, we investigated the impact of altered expression and function of cellular calcium transport mechanisms as occurs in chronic AF on atrial electrophysiology. Methods and Results: In silico experiments were performed in a computational model of the human atrial myocyte. Remodeled function of cellular components was based on a broad review of the literature of in vitro findings in chronic AF, and these were integrated in the model to define a cohort of virtual cells. Simulation results indicate that, while the altered function of calcium and potassium ion channels alone causes a pronounced decrease in action potential duration (APD), remodeling of calcium handling and cellular hypertrophy have a significant additional impact on the reduction of calcium transient (CaT) amplitude in chronic AF. Furthermore, the results suggest that the tight coupling between AP and CaT could be a pharmaceutical target for reversing AP shortening in this context. Finally, we also found that, contrary to a recent hypothesis, that the propensity of delayed afterdepolarizations in the human atrial myocyte was reduced in chronic AF in comparison to normal sinus rhythm. Conclusion: Our results indicate that reduced atrial refractoriness (decreased APD) and loss of contraction (reduced CaT amplitude) are affected not only by modified sarcolemmal ion currents, but also by remodeling of calcium handling and cellular hypertrophy. These findings may have important implications for developing novel therapeutic approaches for chronic AF.},
	keywords = {Conference},
	author = {Koivum{\"a}ki, Jussi and Maleckar, Molly and Tavi, Pasi}
}
@misc {Simula.simula.1710,
	title = {Excitation-Contraction Coupling in Human Atrial Myocytes: Remodeling in Atrial Fibrillation},
	howpublished = {Seminar at the Institute of Biomedical Engineering, KIT, Germany},
	year = {2012},
	month = {February},
	author = {Koivum{\"a}ki, Jussi and Tavi, Pasi}
}
