Modeling the Chronotropic Effect of Isoprenaline on Bio-pacemaker: A Simulation Study

Comparing with traditional electrical pacemaker, one of the superiorities of biological pacemaker (bio-pacemaker) was that it can facilitate chronotropic responses of autonomic nervous regulation. Autonomic nervous regulates intrinsic sinoatrial node (SAN) by two neurotransmitters: isoprenaline and acetylcholine. Here we simulate the chronotropic effect of isoprenaline (ISO) on the pacemaking ability of bio-pacemaker because how the bio-pacemaker response to autonomic nervous regulation is still not clear. In this study, we built an ISO-influenced pacemaker model based on a ventricular pacemaker model. ISO targeted four ionic currents in bio-pacemaker model: $I_{Kr}, I_{Ks},I_{f}$ and $I_{CaL},$ whose effects was referenced from that in SAN. Simulation results showed that an increase in IKr and IKs caused by ISO made maximum diastolic potential more negative, which motivated the activation level of $I_{Na}$, thus accelerated pacemaking rate. ISO can accelerate the action of $I_{f}$ so that promote pacemaking activity. But the increased $I_{CaL}$ have a negative effect on pacemaking cycle length, which is contrary to common sense. We clarified the effect of each current on pacemaking ability in sub-cellular level.