Hyperpolarization-Activated Current, If, in Mathematical Models of Rabbit Sinoatrial Node Pacemaker Cells

A typical feature of sinoatrial (SA) node pacemaker cells is the presence of an ionic current that activates upon hyperpolarization. The role of this hyperpolarization-activated current, I-f, which is also known as the "funny current" or "pacemaker current," in the spontaneous pacemaker activity of SA nodal cells remains a matter of intense debate. Whereas some conclude that I-f plays a fundamental role in the generation of pacemaker activity and its rate control, others conclude that the role of I-f is limited to a modest contribution to rate control. The ongoing debate is often accompanied with arguments from computer simulations, either to support one's personal view or to invalidate that of the antagonist. In the present paper, we review the various mathematical descriptions of I-f that have been used in computer simulations and compare their strikingly different characteristics with our experimental data. We identify caveats and propose a novel model for I-f based on our experimental data.