The pacemaker function of ICC was deduced from morphological studies (Faussone Pellegrini et al., 1977; Thuneberg, 1982), dissection of pacemaker regions experiments (Smith et al., 1987a; Hara et al., 1986; Serio et al., 1991), studies on isolated ICC and SMCs (Langton et al., 1989; Sanders et al., 2014a; Zhu et al., 2009), studies of muscles from animals with loss-of-function mutations in c-Kit signaling (Ward et al., 1994; Ward et al., 1995; Huizinga et al., 1995) and simultaneous impalements of ICC and SMCs (Cousins et al., 2003). This evidence concerns the gene KIT and intrahepatic cholangiocarcinoma.