UC San Diego

Myosin regulatory light chain associates with the motor protein myosin and plays an important but poorly understood role in regulating behavior of cardiac muscle. Mutations to regulatory light chain, including those which affect its phosphorylation by myosin light chain kinase, have been linked to cardiomyopathies. This protein, as well as several others, are linked together by complex structural interactions to form the myofilament system of cardiac muscle. These interactions make it difficult to extend in-vitro results using isolated regulatory light chain to physiologically relevant conditions. The purpose of this work was to formulate and test predictions regarding the effects of light chain phosphorylation on the function of the mammalian left ventrical. An approach combining experiments and computational models was developed and implemented to describe effects of light chain phosphorylation on function of the intact heart