Are we lost in the labyrinth of the sinoatrial node pacemaker mechanism?

Despite extensive electrophysiologic studies performed to date, the ionic mechanisms of sinoatrial node pacemaker activity are unclear. This article highlights three recent topics associated with this issue: (1) sustained inward current (Ist)); (2) the role of Ca2+ release from the sarcoplasmic reticulum; and (3) the role of L-type Ca2+ current (I(Ca,L)). New observations on these topics seem to make the scenario of the pacemaker mechanism increasingly complex. However, such complexity and diversity of ionic events and their orchestration may be important for the sinoatrial node to perform its robust pacemaking activity under a variety of pathophysiologic circumstances.