Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell

We developed an improved mathematical model for a single primary pacemaker cell of the rabbit sinoatrial node. Original features of our model include 1) incorporation of the sustained inward current (I-st) recently identified in primary pacemaker cells, 2) reformulation of voltage- and Ca2+ dependent inactivation of the L-type Ca2+ channel current (I-Ca,I- L), 3) new expressions for activation kinetics of the rapidly activating delayed rectifier K+ channel current (I-Kr), and 4) incorporation of the subsarcolemmal space as a diffusion barrier for Ca2+. We compared the simulated dynamics of our model with those of previous models, as well as with experimental data, and examined whether the models could accurately simulate the effects of modulating sarcolemmal ionic currents or intracellular Ca2+ dynamics on pacemaker activity. Our model represents significant improvements over the previous models, because it can 1) simulate whole cell voltage- clamp data for I-Ca,I- L, I-Kr, and Ist; 2) reproduce the wave-shapes of spontaneous action potentials and ionic currents during action potential clamp recordings; and 3) mimic the effects of channel blockers or Ca2+ buffers on pacemaker activity more accurately than the previous models.