The heartbeat is a sign of life, and not surprisingly it has attracted much interest and curiosity since the early stages of scientific investigation. Even Leonardo da Vinci, in his anatomical studies, realized that rhythmic, restless activity was an intrinsic property of cardiac muscle (92)," As to the heart: it moves itself, and doth never stop, except it be for eternity." In fact, a search for the basis of spontaneous cardiac activity could only be undertaken several centuries after these primitive observations with the development of techniques that allowed the study of the electrical properties of excitable tissues and particularly of cardiac muscle (18, 71, 77, 23). Cardiac pacemaker activity originates in specialized myocytes located in restricted areas of the heart that are characterized by the ability to beat spontaneously even when separated from the rest of the cardiac muscle (24, 106, 103, 11, 81). Voltage-clamp investigation of pacemaker tissue opened the way to a better understanding of the ionic mechanisms promoting rhythmicity in pacemaker tissue (64, 6). In pacemaker cells of the mammalian sino-atrial (SA) node, spontaneous activity results from a typical phase of their action potential, the slow diastolic depolarization. The concept that a slow depolarization is an inherent property of spontaneously active myocar dium is an old one that has been actively investigated since the first recordings of cardiac electrical activity revealed the existence of a slow depolarizing phase preceding the action potential onset in beating tissue (for a review, see 105). During this phase, corresponding to diastole of the cardiac contraction cycle, the membrane slowly depolarizes following termination of an action potential, until threshold for a new action potential is reached. Thus, the