The University of Manchester, School of Physics and Astronomy, Manchester, M13 9PL, UK.
The University of Leeds, School of Biomedical Sciences, Leeds, LS2 9JT, UK.
Sci Rep. 2018 Jun 14;8(1):9159. doi: 10.1038/s41598-018-27069-x.
Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this study we construct a computational model for describing the electrical activity (simple and complex action potentials), intracellular calcium dynamics and mechanical contractions of isolated uterine myocytes from the pregnant rat. The model reproduces variant types of action potentials - from spikes with a smooth plateau, to spikes with an oscillatory plateau, to bursts of spikes - that are seen during late gestation under different physiological conditions. The effects of the hormones oestradiol (via reductions in calcium and potassium selective channel conductance), oxytocin (via an increase in intracellular calcium release) and the tocolytic nifedipine (via a block of L-type calcium channels currents) on action potentials and contractions are also reproduced, which quantitatively match to experimental data. All of these results validated the cell model development. In conclusion, the developed model provides a computational platform for further investigations of the ionic mechanism underlying the genesis and control of electrical and mechanical activities in the rat uterine myocytes.
人类异常的子宫平滑肌活动是主要的健康问题。然而，在妊娠期间维持子宫平滑肌静止以及在分娩时启动和维持长时间子宫收缩的细胞和组织机制尚不完全清楚。在这项研究中，我们构建了一个计算模型，用于描述来自怀孕大鼠的分离子宫平滑肌细胞的电活动（简单和复杂动作电位）、细胞内钙动力学和机械收缩。该模型再现了不同生理条件下妊娠晚期出现的各种类型的动作电位——从具有平滑平台的尖峰到具有振荡平台的尖峰，再到尖峰爆发。该模型还再现了激素雌二醇（通过降低钙和钾选择性通道电导）、催产素（通过增加细胞内钙释放）和保胎药硝苯地平（通过阻断 L 型钙通道电流）对动作电位和收缩的影响，这些影响在数量上与实验数据相匹配。所有这些结果都验证了细胞模型的开发。总之，所开发的模型为进一步研究大鼠子宫平滑肌细胞电和机械活动产生和控制的离子机制提供了一个计算平台。
