窦房结是心脏电活动的起源，其功能不全与房性心律失常间互为因果。揭示窦房结自律性产生的机制及其与心律失常间的关系对临床治疗和药物研发具有重要意义。本课题拟结合计算机仿真的定量电生理研究方法，以及双CCD同步记录膜电位和细胞内钙瞬变的光学标测实验技术手段，在建立的窦房结和心房组织模型上，就窦房结自律性最新提出的钙钟和膜钟的双重机制展开深入研究。揭示钙钟和膜钟的电生理特征，在窦房结舒张期自动除极中的相对作用，对心率、主导起搏位置及节律稳定性的影响；选择性地改变与膜钟相关的离子通道电导，调节钙钟与膜钟的相对关系，诱导窦房结起搏细胞延迟后除极DAD，提出DAD的诱发条件，以及可引起触发激动，进而诱发房性心律失常的机制，揭示钙钟在其中的主要作用；研究窦房结和心房间电活动相互作用的特征，电折返的维持和漂移，揭示房速/房颤时窦房结功能不全的机制。探讨促使房速/房颤自限的方法，为预防和治疗提供指导和理论依据

Sinoatrial node (SAN) is the source of the electrical activity in heats. Its dysfunction has a relationship of reciprocal causation with atrial arrhythmias. Revealling the underlying mechanisms of the automaticity in SAN and their relevance to atrial arrhythmias are significant to the clinical therapy and the medicine developments. In this project, based on the quantitative electrophysiological study method of the computer simulation in combination with the dual-CCD optical mapping technique for simultaneously recording the membrane potential and intracellular calcium, the new concepts of calcium clock and membrane clock mechanisms in sinoatrial nodal automaticity are investigated on the developed SAN and atrial tissue model. The study will reveal electrophysiological characteristics of the calcium and membrane clocks, the relative role of both clocks in the late diastolic depolarization, and their effects on sinus rates, leading pacemaker sites and stability of the rhythm. By selectively changing conductances of the ionic channels associated with the membrane clock, and thus adjusting the relativity of the calcium and membrane clocks to induce the delayed afterdepolarization (DAD) in the SAN, the conditions for DAD occurrence, especially the function of the calcium clock, the subsequent triggered activity and atrial arrhythmias will be investigated. Moreover, the interacting properties of the electrical activity between the SAN and the atrium, and the maintenance and drift of the reentrant waves will also be studied in order to reveal mechanisms of the sinoatrial nodal malfunction during atrial tachycardias (ATs) or atrial fibrillations (AFs). Furthermore, the method of prompting self-termination of ATs/AFs will be investigated in this project to provide guidance and principles for the precaution and treatment of the atrial arrhythmias.