Previous studies have shown dramatic species-differences in the pacemaking action potentials of the rabbit and murine sinoatrial node (SAN) cells, with the latter having much faster pacemking rate (189 vs 294 beats/min), greater upstroke velocity (2.66 vs 9.21 V/s) but shorter action potential duration (169.60 vs 57.66 ms). However, the ionic mechanisms underlying such species-differences in cardiac pacemaking action potentials are unclear. This study aimed to investigate the ionic basis responsible for the differences in the rabbit and murine pacemaking action potentials by using computer models. The biophysically detailed computer models for the rabbit (Zhang et al., 2000) and murine (Kharch et al., 2011) SAN cells were used to investigate the functional impacts of experimentally observed differences in the kinetics and current densities of individual ionic channels between rabbits and mice on their action potentials. Simulation results suggested that the difference in the pacemaking action potentials can be attributable to the differences in the INa, ICaL, ICaT, If, and IKr between the two species. Specifically, the faster pacemaking rate in the murine SAN cells is due to its greater density of INa, ICaT, and If, among which INa plays a key role. The shorter APD in the murine SAN cells is due to the integral action of its larger ICaL and IKr. The faster upstroke velocity in the murine SAN action potentials can be accounted for by the integral effect of its larger INa, ICaL, ICaT and If. In conclusion, this study provides mechanistic insights towards understanding the ionic basis underlying the species-difference in the pacemaking action potentials of the rabbit and murine SANs.
University of Manchester (2012) Proc Physiol Soc 28, PC43
Poster Communications: Ionic mechanisms underlying the difference in the pacemaking action potentials of the rabbit and the murine sinoatrial node cells
R. Wang1, X. Wang2, M. Lei3, M. Boyett3, H. Zhang1
1. Biological Physics Group, The University of Manchester, Manchester, United Kingdom. 2. Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom. 3. Cardiovascular Research Group, The University of Manchester, Manchester, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.