Cardiac pacemaker: 15 years of "new" interpretation.

After more than 15 years since the "new" interpretation of the Purkinje fibre's pacemaker current was proposed, much progress has been made in the understanding of the basic functional principles of cardiac pacemaking. We now know that, in both the SA node and Purkinje fibres, the diastolic depolarization is generated by the interplay of several ionic components, the key process being represented by the turning-on of the hyperpolarization-activated i(f) current towards the end of the action potential repolarization phase. The properties of i(f) are well suited not only to generate, but also to mediate the control of cardiac rate by autonomic transmitters. This control is exerted through modulation of adenylate-cyclase and of cAMP, and allows a fine and rapid adjustment of heart rate to the changing needs of our normal day-life. Still, several problems remain to be clarified : for example, it is not clear how the degree of involvement of i(f) and other components changes in different areas of the nodal region, and whether this process is under control of the autonomic nervous system; more importantly, it is still unknown if the pacemaking mechanisms are similar in the newborn and in the adult, or if developmental changes in the way pacemaker activity is generated and modulated exist.