The rhythmic heart beat is regulated by a precisely timed sequence of pacemaking impulses that propagate through the cardiac conduction system (Tawara, 1906; Goldenberg

The rhythmic heart beat is regulated by a precisely timed sequence of pacemaking impulses that propagate through the cardiac conduction system (Tawara, 1906; Goldenberg and Rothberger, 1936; Bozler, 1942; Fig. 1A). Pacemaking impulses are periodically generated at the sinoatrial node and spread through atrial myocytes initiating contraction of both atrial chambers. The electrical excitation is then received by the atrioventricular (AV) node (Tawara, 1906) and AV-ring. After a slight delay, the impulse rapidly propagates along the AV bundle (His, 1893) and its branched limbs (Tawara, 1906), spreading into the working ventricular muscle through the Purkinje fiber network (Purkinje, 1845; Kolliker, 1902; Tawara, 1906). Cells in the conduction system are distinguished from contractile myocytes by physiological, histological and molecular characteristics (reviewed in Mikawa and Fischman, 1996). In the chick heart, Purkinje fibers are identified as a cellular network that branches out from the AV-bundle, runs subendocardially, and penetrates into the myocardium along the arterial bed (Davies, 1930; Vassal-Adams, 1982; Lamers et al., 1991; Gourdie et al., 1995). The impulse-conducting cells exhibit a unique pattern of gene expression (reviewed in Schiaffino, 1997; Moorman et al., 1998). They upregulate a conduction cell-specific gap-junction protein (Gourdie et al., 1993; Delorme et al., 1995), and genes typically expressed in neuronal (Gorza et al., 1988, 1994; Gourdie et al., 1999) and skeletal muscle cells, such as slow twitch muscle myosin heavy chain (sMyHC) (Sartore et al., 1978; Gonzalez-Sanchez and Bader, 1985), atrial myosin heavy chain (AMyHC) (de Groot et al., 1987) and skeletal muscle myosin binding protein-H (Alyonycheva et al., 1997). Purkinje fibers also downregulate cardiac muscle specific myofibrillar proteins, such as cardiac myosin binding protein-C (cMyBP-C) (Gourdie et al., 1998), which are essential for normal heart muscle contractility (Watkins et al., 1995; Bonne et al., 1995). This unique pattern of gene expression, particularly the 3523 Development 127, 3523-3532 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV4387