The cardiac pacemaker is a sino-atrial (SA) nodal cell. The signal induced by this pacemaker is distributed over the heart surface by a specialised conduction system and is clinically recorded as the ECG. The SA nodal cells are highly resistant to cardiac failure and ischemia. Under calcium overload conditions, some dysrythmias of SA nodal cells occur easily. Morphological analysis under these conditions shows swelling of the cisternae of the Golgi apparatus, with little or no other histological change or damage being observed. The rate of sinus rhythm is quite different between various species. The investigations of SA nodal cells have so far clarified the pacemaker mechanisms involved. A number of ionic channel currents or pacemaker currents, contribute to the depolarization of the pacemaker potential (phase 4). This will not occur with a single current. Recent experiments have identified several novel pacemaker currents and have also revealed several differences in the pacemaker currents between species. The marked hyperpolarization-activated inward current (I(f)) appears in SA nodal cells of most species, while the inwardly rectifying K+ current (I(K1)) with masked I(f) current is found in those of the rat and monkey. In addition, the rapidly activated current (I(Kr)) and slowly activated current (I(Ks)) of the delayed rectifier K+ current (I(K)) contribute to the pacemaker potential in guinea pig SA nodal cells, with only the I(Ks) current in porcine SA nodal cells and only the I(Kr) current in the rat and rabbit. These differences in ionic channels presumably result from differences in gene expression. Some smooth muscle cells also possess the capacity to beat spontaneously. Uterine smooth muscle cells also exhibit an I(f) current. The basal mechanism for spontaneous activity in both SA nodal cells and smooth muscle cells is almost the same, but some differences in the ionic channels and their genetic expression may contribute to their respective pacemaker currents.