ABSTRACT
Although the mechanistic link between variations in intracellular calcium and its effects on myofilament regulatory proteins and subsequent impact on cardiac muscle force production have been known for some time, characterization of cardiac contractile properties are predominantly confined to phenomenological descriptions of the relationship between either muscle length and force or ventricular pressure and volume. However, as recognition of the limitations of these theories grow, investigators have begun to look toward more fundamental theories of cardiac contraction to explain whole heart function. The goal of the present study was first to explore, on a theoretical level, the degree of complexity required in a biochemical model necessary to adequately explain both equilibrium and twitch contraction behavior of cardiac muscle. Central to this analysis was a critical examination of the evidence for and against the importance of a calcium-free, force-generating state. Next, we determined whether such theories can actually account for the interrelationships between the experimentally measured time courses of pressure generation and the calcium transient measured from intact ventricles during both normal twitches as well as during complex contraction sequences. The results of this analysis provide strong support for a four-state model, including the calcium-free, force-generating state. These results will help guide the continuing quest for a mechanistic theory of ventricular function.
