The Ionic Currents Underlying Pacemaker Activity

Abstract

Rhythmic activity is a typical feature of the living heart. While in most other excitable tissues the generation of the action potential usually follows some kind of stimulation, in the heart a sustained repetitive firing is the normal working condition. In the mammalian heart, pacemaking originates from a well-defined region in the right atrium, the sino-atrial node, also called the heart pacemaker. Because of its special features and its obvious importance in heart activity, pacemaking attracted the interest of early cardiac electrophysiologists, who tried to establish the nature of the underlying mechanism. Early single-microelectrode experiments and subsequent voltage-clamp experiments led to the view that, at least in the Purkinje fiber, pacemaking was associated with the decay of a pure K current deactivating on hyperpolarization which, at the end of an action potential, tended to slowly depolarize the membrane and bring it up to the threshold for a new action potential. Since that first interpretation, a great deal of new experimental data has been produced and new ideas have been put forward. It is the aim of this paper to review some of the steps that have led to the present views on the origin of cardiac pacemaking, further extending the recent reviews of Brown (1) and Noble (2).