Automaticity Control by Membrane and Calcium Clocks in Ischemic Sinoatrial Node
1 School of Electrical Engineering, Xi’an Jiaotong University, Xi’an 710049, China
2 Cardiology Department, the First Hospital, Xi’an Jiaotong University, Xi’an 710061, China
3 School of Mathematics and Statistics, Xi’an Jiaotong University, Xi’an 710049, China
Abstract：Ischemiainduced sinus bradycardia and beating pause are commonly occurred in clinics, but its ionic mechanisms are still not very clear. Based on the action potential dynamic model of the sinoatrial node cell (SANC), and by increasing the extracellular K+ and intracellular Na+ concentrations, enhancing Ltype Ca2+ current ICaL, decreasing NaCa exchange current INCX and Ttype Ca2+ current ICaT, we simulated the ischemia and quantitatively studied the role of individual factor in SANC automaticity. Additionally, by developing a onedimensional SANatrium tissue model on the monodomain equation, the electrical propagation state and role of calcium clock were studied as well. Results showed that during ischemia the enhanced ICaL and accumulation of K+ had little impacts on automaticity. Although decreasing ICaT by one time caused 13% drop in beating frequency, automaticity still remained. However, potential oscillation and even beating pause were found after elevating intracellular Na+by 10% or reducing INCX by 55%. Further study showed that the impact of intracellular Na+on automaticitywas actually realized through the indirect decrease of INCX.Therefore, we suggest that reduction of INCX is a crucial factor to cause sinus bradycardia and even pause during ischemia. In addition, during ischemia, the automaticity was able to recover through enhancing calcium clock activity, suggesting the synergistic membrane and calcium clocks are fundamentals to the automatic depolarization of SANC.
