THE CARDIAC-PACEMAKER CURRENT IF

Since the hyperpolarization-activated current, i(f), was originally associated with the diastolic depolarization phase of action potential in the sinoatrial (SA) node in 1979, its central role in the generation and control of pacemaker activity has become increasingly clear through a series of experimental findings, some of which have substantially modified the pre-existing theories of cardiac pacemaking and its modulation by the autonomic transmitters. Thus, the pacemaker current of Purkinje fibers, formerly described as a deactivating pure potassium (K) current, was found to be in fact, like the nodal i(f), inward and activating on hyperpolarization. Furthermore, in SA node cells, as well as mediating rhythm acceleration induced by catecholamines, i(f) was found to underlie the slowing effect of low acetylcholine (ACh) concentrations, in contrast with the generally accepted hypothesis that activation of a K conductance is the main process responsible for cardiac slowing. A final, atypical property of i(f) recently demonstrated concerns the activating action exerted on i(f) by intracellular cAMP. Unlike that on other voltage-gated, cAMP-modulated cardiac channels, this action is independent of phosphorylation and involves a direct binding of cAMP to i(f) channels.