Thomas Kandace, Henley Trevor, Rossi Simone, Costello M Joseph, Polacheck William, Griffith Boyce E, Bressan Michael
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Mathematics, University of North Carolina, Chapel Hill, NC, USA.
Dev Cell. 2021 May 17;56(10):1498-1511.e7. doi: 10.1016/j.devcel.2021.04.004. Epub 2021 Apr 22.
Cardiac pacemaker cells (CPCs) rhythmically initiate the electrical impulses that drive heart contraction. CPCs display the highest rate of spontaneous depolarization in the heart despite being subjected to inhibitory electrochemical conditions that should theoretically suppress their activity. While several models have been proposed to explain this apparent paradox, the actual molecular mechanisms that allow CPCs to overcome electrogenic barriers to their function remain poorly understood. Here, we have traced CPC development at single-cell resolution and uncovered a series of cytoarchitectural patterning events that are critical for proper pacemaking. Specifically, our data reveal that CPCs dynamically modulate adherens junction (AJ) engagement to control characteristics including surface area, volume, and gap junctional coupling. This allows CPCs to adopt a structural configuration that supports their overall excitability. Thus, our data have identified a direct role for local cellular mechanics in patterning critical morphological features that are necessary for CPC electrical activity.
心脏起搏器细胞（CPCs）有节奏地引发驱动心脏收缩的电冲动。尽管处于理论上应抑制其活动的抑制性电化学条件下，但CPCs在心脏中表现出最高的自发去极化速率。虽然已经提出了几种模型来解释这一明显的矛盾现象，但对于使CPCs克服其功能的电生障碍的实际分子机制仍知之甚少。在这里，我们以单细胞分辨率追踪了CPCs的发育过程，并发现了一系列对于正常起搏至关重要的细胞结构模式形成事件。具体而言，我们的数据显示，CPCs动态调节黏附连接（AJ）的参与，以控制包括表面积、体积和间隙连接耦合等特征。这使得CPCs能够采用一种支持其整体兴奋性的结构构型。因此，我们的数据确定了局部细胞力学在塑造CPCs电活动所需的关键形态特征方面的直接作用。
