Development and testing of Cardiac Physiome cell model parts in skeletal muscle
Seminar Room 1, Newton Institute
In the living heart, the dynamic range of ATP turnover and associated oxygen consumption is relatively small - one order of magnitude - while metabolic homeostasis is highly robust (1). As a result, it has proven difficult to obtain in vivo dynamic data on ATP metabolism in the heart complicating parameterization and testing of computational models of cardiac energy metabolism. Typically, only steady-state data have been available to this aim (2, 3). In skeletal muscle, the situation is quite the opposite. The myofiber metabolic networks may undergo up to 500-fold changes in ATP turnover rate between rest and all-out sprint (4). These changes in ATP turnover rate are accompanied by very significant concentration changes in intermediairy metabolites such as the ATP hydrolysis products and glycolytic intermediates that can be tracked non-invasively using NMR spectroscopic techniques (4). Since the metabolic networks in cardiac and oxidative skeletal muscle fibers that supply the cell with ATP are to a large extend homologous (5), skeletal muscle provides a valuable experimental system to test and develop computational cell model parts for the Cardiac Physiome (6). Here, we report on the progress we have made in testing and development of computational models of mitochondrial oxidative metabolism and electrophysiology (Beard model) and glycogenolysis (Lambeth & Kushmerick model) and their integration in space and time.