Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, 63130, USA.
Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, 63130, USA.
Sci Rep. 2020 Oct 1;10(1):16221. doi: 10.1038/s41598-020-72562-x.
As the uterus remodels in preparation for delivery, the excitability and contractility of the uterine smooth muscle layer, the myometrium, increase drastically. But when remodelling proceeds abnormally it can contribute to preterm birth, slow progress of labour, and failure to initiate labour. Remodelling increases intercellular coupling and cellular excitability, which are the main targets of pharmaceutical treatments for uterine contraction disorders. However, the way in which electrical propagation and force development depend on intercellular coupling and cellular excitability is not fully understood. Using a computational myofibre model we study the dependency of electrical propagation and force development on intercellular coupling and cellular excitability. This model reveals that intercellular coupling determines the conduction velocity. Moreover, our model shows that intercellular coupling alone does not regulate force development. Further, cellular excitability controls whether conduction across the cells is blocked. Lastly, our model describes how cellular excitability regulates force development. Our results bridge cellular factors, targeted by drugs to regulate uterine contractions, and tissue level electromechanical properties, which are responsible for delivery. They are a step forward towards understanding uterine excitation-contraction dynamics and developing safer and more efficient pharmaceutical treatments for uterine contraction disorders.
随着子宫为分娩做准备而重塑，子宫平滑肌层（即子宫肌层）的兴奋性和收缩性会急剧增加。但是，如果重塑过程异常，可能会导致早产、分娩进展缓慢以及分娩启动失败。重塑会增加细胞间耦合和细胞兴奋性，这是治疗子宫收缩障碍的药物的主要靶点。然而，电传播和力发展依赖于细胞间耦合和细胞兴奋性的方式尚未完全了解。我们使用计算肌纤维模型研究了电传播和力发展对细胞间耦合和细胞兴奋性的依赖性。该模型表明，细胞间耦合决定了传导速度。此外，我们的模型还表明，细胞间耦合本身并不能调节力的发展。进一步地，细胞兴奋性控制着细胞间的传导是否被阻断。最后，我们的模型描述了细胞兴奋性如何调节力的发展。我们的研究结果将药物靶向调节子宫收缩的细胞因子与负责分娩的组织水平机电特性联系起来。这些结果是朝着理解子宫兴奋-收缩动力学和开发更安全、更有效的子宫收缩障碍药物治疗方法迈出的一步。
