Modeling the chronotropic effect of isoprenaline on bio-pacemaker: A Simulation Study

Yacong Li1, Kuanquan Wang1, Qince Li1, Henggui Zhang2
1Harbin Institute of Technology, 2University of Manchester


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: IKr, IKs, If and ICaL, 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 INa, thus accelerated pacemaking rate. ISO can accelerate the action of If, so that promote pacemaking activity. But the increased ICaL 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.