抄録
The cardiac biological pacemaker (BP) has been created by suppression of the inward-rectifier K+ current (IK1) or overexpression of the hyperpolarization-activated current (Ih) in ventricular (Purkinje) or atrial myocytes, suggesting possible development of the functional BP as a therapeutic alternative to the electronic pacemaker. In this study, we investigated the effects of incorporating regulatory inward currents (pacemaker currents) such as Ih, sustained inward current (Ist), and low voltage-activated L-type Ca2+ channel current (ICa,LD) on 1) creation of BP cells, 2) robustness of BP activity to electrotonic loads of adjacent non-pacemaker cells, and 3) BP cell ability to drive the surrounding non-pacemaker cells. Bifurcation structures of single BP cell and coupled-cell models for human ventricular myocytes (HVMs) were explored during changes in conductance of IK1, the regulatory inward currents, and gap junction. Our findings suggest that 1) incorporating Ih and Ist (or Ih and ICa,LD) facilitates BP generation during IK1 suppression, although it does not lead to BP oscillation without IK1 inhibition, and that 2) incorporating Ist or ICa,LD significantly improve the structural stability of BP cells to electrotonic loads and BP cell ability to drive adjacent HVMs. [J Physiol Sci. 2006;56 Suppl:S129]
