Mechanism for Triggered Waves in Atrial Myocytes.
Mechanism for Triggered Waves in Atrial Myocytes.
复制标题
心房肌细胞触发波的机制。
DOI：
10.1016/j.bpj.2017.06.026
复制
发表时间：
2017
影响因子：
3.4
通讯作者：
Wasserstrom,JAndrew
中科院分区：
文献类型：
--
作者：
Shiferaw,Yohannes;Aistrup,GaryL;Wasserstrom,JAndrew
心房细胞兴奋-收缩偶联是由L型钙通道和Ryanodine受体之间的钙信号介导的，主要发生在细胞边界。这种独特的结构决定了正常和疾病条件下Ca信号传导的基本方面。在这项研究中，我们应用激光扫描共聚焦显微镜，沿着与实验为基础的计算模型，了解钙循环动力学的心房细胞进行快速起搏。我们的主要发现是，当心房细胞起搏钙超载条件下，钙波可以在细胞边界上的核和传播到细胞内部。这些传播的Ca波被称为“触发波”，因为它们在动作电位期间由L型Ca通道开放引发。这些激发不同于起源于Ryanodine受体通道的随机波动的自发Ca波，并且其发生在更长的等待时间之后。此外，我们认为，这些触发波的发病是一个高度非线性的肌浆网钙负荷的功能。这种强非线性导致快速起搏频率下Ca的非周期性反应，这是由起搏Ca释放和触发波之间的复杂相互作用引起的。我们进一步认为，心房细胞的这一特点导致动态不稳定，可能是房性心律失常的基础。这些研究将作为探索心房细胞非线性动力学的起点，并将深入了解心房颤动的触发和维持。
Excitation-contraction coupling in atrial cells is mediated by calcium (Ca) signaling between L-type Ca channels and Ryanodine receptors that occurs mainly at the cell boundary. This unique architecture dictates essential aspects of Ca signaling under both normal and diseased conditions. In this study we apply laser scanning confocal microscopy, along with an experimentally based computational model, to understand the Ca cycling dynamics of an atrial cell subjected to rapid pacing. Our main finding is that when an atrial cell is paced under Ca overload conditions, Ca waves can then nucleate on the cell boundary and propagate to the cell interior. These propagating Ca waves are referred to as "triggered waves" because they are initiated by L-type Ca channel openings during the action potential. These excitations are distinct from spontaneous Ca waves originating from random fluctuations of Ryanodine receptor channels, and which occur after much longer waiting times. Furthermore, we argue that the onset of these triggered waves is a highly nonlinear function of the sarcoplasmic reticulum Ca load. This strong nonlinearity leads to aperiodic response of Ca at rapid pacing rates that is caused by the complex interplay between paced Ca release and triggered waves. We argue further that this feature of atrial cells leads to dynamic instabilities that may underlie atrial arrhythmias. These studies will serve as a starting point to explore the nonlinear dynamics of atrial cells and will yield insights into the trigger and maintenance of atrial fibrillation.