Fig. 8. Model for age-dependent differentiation of Purkinje fibers from embryonic myocytes induced by local production of ET ligand and its interaction with ET receptor. In the embryonic chicken heart, there are two types of endothelial cells: ECE-expressing and non-expressing cells. Only the former convert bigET into mature ET. Among ET receptor (ETR)-positive myocytes, only those adjacent to ET production can be induced to differentiate into conduction cells. As embryonic development proceeds, the level of ET receptors in myocytes declines, resulting in the loss of competency to respond to ET ligand and to differentiate into conduction cells.