@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}
}
