Generation and control of cardiac pacing the pacemaker current

Several currents contribute to the electrical activity of mammalian pacemaker cells. Of these, the hyperpolarization-activated current, i(f), is involved in the generation of the diastolic depolarization phase, and therefore has a main role in controlling the most peculiar feature of these cells: their ability to beat spontaneously and to drive the heartbeat. More than this, i(f) represents the key mechanism by which sympathetic and parasympathetic stimuli regulate, via the diastolic depolarization phase, the pacing frequency of sinoatrial node cells and thus the heart rate. This is achieved through regulation of adenylyl-cyclase activity and of intracellular cAMP, which is the second messenger in i(f) modulation. A fine regulation of i(f) is thus the basis by which epinephrine and acetylcholine exert their fine control on cardiac rhythm.