抄録
We investigated the dynamical mechanisms of biological pacemaker (BP) generation in human ventricular myocytes (HVMs) by bifurcation analyses of a mathematical model. Equilibrium points (EPs), periodic orbits, stability of EPs, and bifurcation points were calculated as functions of conductance or amplitude of inward-rectifier K+ current (IK1), L-type Ca2+ current (ICa,L), delayed-rectifier K+ current (IK), Na+-Ca2+ exchanger current (INaCa) or constant bias current (Ibias) for constructing bifurcation diagrams. Pacemaker activity (stable limit cycle) abruptly appeared around an unstable EP via a saddle-node bifurcation, when IK1 was suppressed by 84.6%. After the bifurcation, the IK1-downregulated HVM has an unstable EP only, which is essentially important for stable BP generation. To elucidate how individual sarcolemmal currents contribute to EP instability and BP generation, we further explored the bifurcation structures of the system during decreases in each current. Our results suggest that 1) IK1 suppression is necessary for creation of the BP cell system, 2) ICa,L is, but IK or INaCa is not, responsible for EP instability as a requisite for stable BP generation, 3) IK is indispensable for robust pacemaking with large amplitude, high upstroke velocity and stable frequency, and 4) INaCa is the dominant pacemaker current, but not necessarily required for BP oscillations. [Jpn J Physiol 55 Suppl:S91 (2005)]
