Homogeneity out of heterogeneity.

T hree different mechanisms are now recognized as participating in the regulation of cardiac function1: by changing end-diastolic fiber length (Starling's law of the heart), by biochemical changes occurring within the myocardial cell (myocardial contractility), and by altered gene expression (molecular biology). Each plays a distinct role in allowing cardiac function to respond to the changing demands that the body places on the cardiovascular system. Starling's law of the heart, which operates at the organ level, regulates the output of the heart on a beat-to-beat basis by adjusting cardiac work capacity to changes in preload and afterload. Changing myocardial contractility regulates cardiac performance over a slower time course, largely by altering the Ca2` fluxes involved in excitation-contraction coupling; this second mechanism allows individual myocardial cells to respond to humoral stimuli such as the sympathetic neurotransmitters released during exercise. Regulation by altered gene expression, the third mechanism, alters myocardial function over an even slower time course in that changing protein composition facilitates the cardiac response to sustained changes in cardiovascular function that occurs in endocrinopathies, aging, and chronic hemodynamic overloading.2-4 We describe an additional role for regulation by altered gene expression in an effort to clarify the significance of the remarkable cellular and molecular heterogeneity in the heart. Using the ancient Greek trireme as a model we illustrate the manner by which the cellular and molecular heterogeneity made possible by variable gene expression underlies the remarkable homogeneity of function of the heart as an organ.