Sustained inward current and pacemaker activity of mammalian sinoatrial node

A novel sustained inward Na+ current i(sv), which sensitive to Ca2+-antagonists and potentiated by beta-adrenergic stimulation, has been described in pacemaker cells of rabbit, guinea pig, and rat sinoatrial node, as well as rabbit AV node. Although i(st) has been suggested to be an important pacemaker current, this has never been tested experimentally because of the lack of a specific blocker. In this study, we address the role of i(st) in the pacemaker activity of the sinoatrial node cell using computer models.

The newly developed models of Zhang et al. for peripheral and central rabbit sinoatrial node cells and models of Noble and Noble, Demir et al., Wilders et al., and Dokos et al. for typical rabbit sinoatrial node cells were modified to incorporate equations for i(st). The conductance g(st) was chosen to give a current density-voltage relationship consistent with experimental data. In the models of Zhang et al. (periphery), Noble and Noble, and Dokos et al., in which i(st) was smaller or about the same amplitude as other inward currents, i(st) increased the pacemaking rate by 0.6%, 2.2%, and 0.8%, respectively. In the models of Zhang et al. (center), Demir et al., and Wilders et al., in which i(st) was larger than some other inward ionic currents, i(st) increased the pacemaking rate by 7%, 20%, and 14%, respectively.

i(st) has the potential to be a regulator of pacemaker activity, although its importance will depend on the amplitude of i(st) relative to the amplitude of other inward currents involved in pacemaker activity.