Activation in Cardiac Muscle

W hen a muscle is stimulated electrically, its ability to contract rises and then falls. It is conceptually easy to imagine, therefore, that something called the "active state" might rise and fall with a well-defined time course. Although the concept is simple, the attempts to measure this time course have produced such conflicting results that the whole concept has fallen into disrepute.1 These conflicting results generally are attributed to the fact that the perturbations used to make the measurements frequently altered the active state. Another good reason is that many different parameters were being measured as a reflection of the active state, and some of them may have been inappropriate. As a result, the terms "active state" and "activation" became imprecise and vague, even though they have remained in general use and embody a potentially useful concept. As the concept of active state became more imprecise, interest among muscle physiologists shifted away from this area to studies of the individual mechanisms responsible for activation. These newer studies were made possible by the development of chemical techniques that permitted the exploration of molecular mechanisms. Many of these mechanisms now have been elucidated, and the first purpose of this review is to describe them. This description leads to a definition of what is meant, and what is not meant, by the term "activation." The second, and major, purpose of this review is to examine the changes in contractile properties of muscle that accompany changes in activation. In the course of this examination, an effort will be made to define mechanical parameters that signal changes in activation. As with the first section, emphasis will be given to showing that some parameters do not accurately signal changes in activation. A third and final purpose of the article is to review the history of the