Cycle length restitution in sinoatrial node cells: a theory for understanding spontaneous action potential dynamics.
Cycle length restitution in sinoatrial node cells: a theory for understanding spontaneous action potential dynamics.
复制标题
DOI：
10.1371/journal.pone.0089049
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hund TJ
中科院分区：
文献类型：
--
作者：
Glynn P;Onal B;Hund TJ
正常心律（窦性心律）由窦房结控制，窦房结是右心房中自发活动的肌细胞的特化和高度异质性集合。以缓慢和/或异步起搏器活动甚至失败为特征的窦房结功能障碍与心血管疾病（例如心力衰竭、房颤）相关。虽然在了解窦房结细胞自律性的分子和离子基础方面取得了巨大进展，但支配窦房结细胞同步性和整体起搏器功能的动力学仍不清楚。在这里，一个经过充分验证的小鼠窦房结细胞的计算模型被用来测试假设，窦房结细胞动力学反映了固有的恢复属性（周期长度恢复），可能会引起广泛的行为，从规则的周期性，高度复杂的，不规则的激活。进行计算机模拟，以确定使用新定义的电压脉冲协议的计算模型中的周期长度恢复曲线。恢复曲线预测窦房结细胞动力学的能力（例如，不规则自发活动的出现）和对终止的敏感性。最后，离子和组织水平的因素（如离子通道电导，离子浓度，细胞与细胞的耦合），影响恢复和窦房结细胞动力学进行了探讨。总之，这些研究结果表明，周期长度恢复可能是一个有用的工具，用于分析细胞动力学和功能障碍的窦房结。
Normal heart rhythm (sinus rhythm) is governed by the sinoatrial node, a specialized and highly heterogeneous collection of spontaneously active myocytes in the right atrium. Sinoatrial node dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, is associated with cardiovascular disease (e.g. heart failure, atrial fibrillation). While tremendous progress has been made in understanding the molecular and ionic basis of automaticity in sinoatrial node cells, the dynamics governing sinoatrial nodel cell synchrony and overall pacemaker function remain unclear. Here, a well-validated computational model of the mouse sinoatrial node cell is used to test the hypothesis that sinoatrial node cell dynamics reflect an inherent restitution property (cycle length restitution) that may give rise to a wide range of behavior from regular periodicity to highly complex, irregular activation. Computer simulations are performed to determine the cycle length restitution curve in the computational model using a newly defined voltage pulse protocol. The ability of the restitution curve to predict sinoatrial node cell dynamics (e.g., the emergence of irregular spontaneous activity) and susceptibility to termination is evaluated. Finally, ionic and tissue level factors (e.g. ion channel conductances, ion concentrations, cell-to-cell coupling) that influence restitution and sinoatrial node cell dynamics are explored. Together, these findings suggest that cycle length restitution may be a useful tool for analyzing cell dynamics and dysfunction in the sinoatrial node.
登录
查看更多内容
影响因子：
37.8
作者：
Koval OM;Snyder JS;Wolf RM;Pavlovicz RE;Glynn P;Curran J;Leymaster ND;Dun W;Wright PJ;Cardona N;Qian L;Mitchell CC;Boyden PA;Binkley PF;Li C;Anderson ME;Mohler PJ;Hund TJ
通讯作者：
Hund TJ
影响因子：
37.8
作者：
Sanders, P;Kistler, PM;Kalman, JM
通讯作者：
Kalman, JM
影响因子：
37.8
作者：
SMITH, JM;CLANCY, EA;COHEN, RJ
通讯作者：
COHEN, RJ
影响因子：
158.5
作者：
ROSENBAUM, DS;JACKSON, LE;COHEN, RJ
通讯作者：
COHEN, RJ
DOI：
10.1152/ajpheart.01050.2002
发表时间：
2003-12-01
影响因子：
4.8
作者：
Kurata, Y;Hisatome, I;Shibamoto, T
通讯作者：
Shibamoto, T