Regional Difference in Dynamical Property of Sinoatrial Node Pacemaking: Role of Na+ Channel Current

To elucidate the regional differences in sinoatrial node pacemaking mechanisms, we investigated 1), bifurcation structures during current blocks or hyperpolarization of the central and peripheral cells, 2), ionic bases of regional differences in bifurcation structures, and 3), the role of Na+ channel current (INa) in peripheral cell pacemaking. Bifurcation analyses were performed for mathematical models of the rabbit sinoatrial node central and peripheral cells; equilibrium points, periodic orbits, and their stability were determined as functions of parameters. Structural stability against applications of acetylcholine or electrotonic modulations of the atrium was also evaluated. Blocking L-type Ca2+ channel current (ICa,L) stabilized equilibrium points and abolished pacemaking in both the center and periphery. Critical acetylcholine concentration and gap junction conductance for pacemaker cessation were higher in the periphery than in the center, being dramatically reduced by blocking INa. Under hyperpolarized conditions, blocking INa, but not eliminating ICa,L, abolished peripheral cell pacemaking. These results suggest that 1), ICa,L is responsible for basal pacemaking in both the central and peripheral cells, 2), the peripheral cell is more robust in withstanding hyperpolarizing loads than the central cell, 3), INa improves the structural stability to hyperpolarizing loads, and 4), INa-dependent pacemaking is possible in hyperpolarized peripheral cells.