Hyperpolarization-Activated ‘Pacemaker Current’ — A Funny Current in Models of SA Nodal Pacemaker Cells

A typical feature of sinoatrial (SA) nodal pacemaker cells is the presence of an ionic current that activates upon hyperpolarization. The contribution of this hyperpolarization-activated current, If, which is also known as the ‘funny current’ or ‘pacemaker current’, to the spontaneous pacemaker activity of SA nodal cells remains a matter of intense debate. We used experimentally recorded action potentials of a single isolated rabbit SA nodal pacemaker cell to reconstruct the time course of If according to the mathematical models of Maltsev and Lakatta (2009) and Severi et al. (2012). The thus reconstructed If was compared to that obtained with a simple and straightforward first-order Hodgkin and Huxley-type model of If based on experimental data acquired in our laboratory. In terms of steady-state activation and fully-activated current amplitude, the model of Maltsev and Lakatta (2009) better fits our experimental data than that of Severi et al. (2012). However, with both models, the reconstructed time course of If shows several discrepancies with the time course based on our experimental data, which is largely due to the almost instantaneous deactivation of If at depolarized potentials in either model.