This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Integrated understanding of cardiac function requires detailed information about a many dynamically interacting systems. We propose to build a detailed quantitative model of rabbit and rat cardiac muscle, which will include electrophysiological properties (e.g. ion channels and transporters), cellular calcium regulation (including calcium currents, sarcoplasmic reticulum calcium uptake and release, sodium/calcium exchange) and contractile activation and relaxation (including myofilament proteins and their cooperative activation by calcium and each other). These models will also be formulated to be appropriate for multiscale integrative analysis spanning cellular to organ scales and physiological timescales. The laboratories of Drs. Bers, McCulloch and their collaborators in Chicago and San Diego have extensive track records of complementary quantitative experiment and analysis. We have an initial functional model already constructed and have made good progress in collaboration with the NBCR in extending it both functionally (to include beta adrenergic regulation) and structurally (to tissue and whole organ scales). In collaboration with La Jolla investigators, the Chicago group will also take advantage of new software tools being developed by the NBCR to allow the new models to be composed and executed interactively, integrated into tissue continuum models and stored using a standardized encoding.
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