Developmental Changes in the Excitation-Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals.

ABSTRACT

The developmental changes in the excitation-contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in the guinea pig it decreases during the fetal stage but turns into an increase just before birth. Such changes can be attributed to changes in the repolarizing potassium currents. The T-tubule and the sarcoplasmic reticulum are scarcely present in the fetal cardiomyocyte, but increase during postnatal development. This causes a developmental shift in the Ca2+ handling from a sarcolemma-dependent mechanism to a sarcoplasmic reticulum-dependent mechanism. The sensitivity for beta-adrenoceptor-mediated positive inotropy decreases during early postnatal development, which parallels the increase in sympathetic nerve innervation. The alpha-adrenoceptor-mediated inotropy in the mouse changes from positive in the neonate to negative in the adult. This can be explained by the change in the excitation-contraction mechanism mentioned above. The shortening of the action potential duration enhances trans-sarcolemmal Ca2+ extrusion by the Na+-Ca2+ exchanger. The sarcoplasmic reticulum-dependent mechanism of contraction in the adult allows Na+-Ca2+ exchanger activity to cause negative inotropy, a mechanism not observed in neonatal myocardium. Such developmental studies would provide clues towards a more comprehensive understanding of cardiac function.