窦房结膜钟和钙钟在缺血条件下对细胞自律性的调控  

Automaticity Control by Membrane and Calcium Clocks in Ischemic Sinoatrial Node

作　　者：张虹[1] 杨琳[2] 赵炜[3] 郑霄[1] 

机构地区：[1]西安交通大学电气工程学院,西安710049 [2]西安交通大学第一附属医院心内科,西安710061 [3]西安交通大学数学和统计学院,西安710049

出　　处：《中国生物医学工程学报》2013年第4期411-417,共7页Chinese Journal of Biomedical Engineering

基　　金：国家自然科学基金(81271661;30971221);教育部回国留学基金(第40批);中央高校基本科研业务费专项资金(08143020)

摘　　要：急性心肌缺血导致的窦性心动过缓甚至停搏在临床上较为常见,但对其微观机制尚缺乏足够的认识。在窦房结细胞动作电位动力学数学模型的基础上,通过提高胞外K+和胞内Na+浓度,增强L-型Ca2+电流ICaL,降低Na-Ca交换电流INCX以及T-型Ca2+电流ICaT模拟缺血,定量研究各因素对起搏细胞自律性的作用。另外,基于单域方程构建一维窦房结及心房组织模型,研究窦房结缺血时组织中的电传导状态以及钙钟的作用。结果表明,缺血时ICaL的增强以及胞外K+浓度的蓄积对自律性并无明显的影响。ICaT降低1倍后尽管可使起搏频率降低13%,而自律性仍可维持。但是,当细胞内Na+升高10%,或INCX减小55%后,会出现电位的振荡乃至停搏。进一步的研究说明,胞内Na+的蓄积间接地通过降低INCX对自律性产生调控作用。因此,INCX的降低应是缺血时造成窦性心动过缓及停搏的主要原因。研究表明,在缺血条件下,增强钙钟的活动有助于自律性和电传导的恢复,表明膜钟和钙钟的相互作用仍是构成细胞自动除极的重要基础。Ischemia-induced 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 L-type Ca2＋ current /CaL, decreasing Na-Ca exchange current INcx and T-type Ca2 ＋ current /CaT , we simulated the ischemia and quantitatively studied the role of individual factor in SANC automatieity. Additionally, by developing a one- dimensional SAN-atrium 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 Ic,L and accumulation of K＋had little impacts on automaticity. Although decreasing Ic, by one time caused 13% drop in heating frequency, automaticity still remained. However, potential oscillation and even heating pause were found after elevating intracellular Na＋ by 10% or reducing INcx by 55%. Further study showed that the impact of intracellular Na ＋ on automatieity was actually realized through the indirect decrease of INcx. Therefore, we suggest that reduction of INcx is a crucial factor to cause sinus bradyeardia 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.

关 键 词：窦房结 膜钟 钙钟 缺血 动作电位模型 

分 类 号：R318.08[医药卫生—生物医学工程]