Induction and patterning of the Purkinje fiber network

Our studies in the embryonic chick heart have shown that impulse-conducting Purkinje cells differentiate from myocytes during embryogenesis. This conversion of contractile myocytes into conduction cells is induced by paracrine signals, such as endothelin (ET), derived from the endocardium and developing coronary arteries. Active ET is secreted through proteolytic processing from its precursor by ET-converting enzyme-1 (ECE-1) and triggers signaling by binding to its receptors. In the embryonic heart, two ET receptors, ETA and ETB, are expressed by myocytes. ECE-1 is predominantly expressed in endothelial cells of the endocardium and coronary arteries, but not in veins or capillaries. Furthermore, retroviral co-expression of exogenous ECE-1 with ET precursor in the embryonic heart is sufficient to induce ectopic myocyte conversion to conduction cells. Thus, localized expression of ECE-1 in endocardial and arterial endothelia is a key mechanism defining the site of Purkinje fiber recruitment in the embryonic myocardium. Inhibition of endogenous ECE-1 expression via suppression of stretch-sensitive channels results in down-regulated expression of Purkinje fiber markers. This finding suggests that biophyical forces acted on, and created by, the cardiovascular system during embryogenesis may play a critical role in induction and patterning of Purkinje fibers.