Loftus Fiona C, Richardson Magnus J E, Shmygol Anatoly
Warwick Systems Biology Centre, University of Warwick, Coventry, UK; Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Coventry, UK; Warwick Systems Biology Doctoral Training Centre, University of Warwick, Coventry, UK.
Warwick Systems Biology Centre, University of Warwick, Coventry, UK.
J Biomech. 2015 Jun 25;48(9):1620-4. doi: 10.1016/j.jbiomech.2015.01.046. Epub 2015 Feb 8.
Elucidation of cellular mechanisms regulating myometrial contractility is crucial for improvement in management of many obstetric abnormalities, such as premature delivery, uterine dystocia and post-partum haemorrhage. Myometrial contractions are triggered by periodic synchronous rises in intracellular calcium concentration ([Ca(2+)]i) elicited by spontaneously generated action potentials propagating throughout the entire myometrium. During labour, hormones like oxytocin and prostaglandins potentiate uterine contractions by increasing their duration, strength and frequency. The most informative approach to studying the mechanisms underlying hormonal modulation of uterine contractility is to record [Ca(2+)]i responses to hormones in intact myometrial samples that have not been subjected to enzymatic treatment for cell isolation or cell culture conditions. However, the spatio-temporal resolution of such recording is limited due to the motion artifacts occurring in contracting tissue. Here we describe the application of our newly developed motion correction algorithm to investigate the [Ca(2+)]i dynamics in control and oxytocin stimulated slices of human myometrium on a cellular level. We present evidence that oxytocin induces asynchronous [Ca(2+)]i oscillations in individual myocytes within intact myometrium which are similar to those observed in cultured cells. The oscillations occur between synchronous action potential-driven [Ca(2+)]i transients but appear to be unrelated to contractions. Furthermore, the oxytocin-triggered [Ca(2+)]i oscillations wane within 30-50min of hormone application, while the action potential induced [Ca(2+)]i transients remain augmented. We conclude that oxytocin-induced [Ca(2+)]i oscillations are not relevant to the acute regulation of myometrial contractility but may play a role in longer-term regulatory processes, for example, by triggering gene expression.
阐明调节子宫肌层收缩性的细胞机制对于改善许多产科异常情况的管理至关重要，如早产、子宫难产和产后出血。子宫肌层收缩是由自发产生的动作电位在整个子宫肌层传播引发的细胞内钙浓度（[Ca(2+)]i）周期性同步升高所触发的。在分娩过程中，催产素和前列腺素等激素通过增加子宫收缩的持续时间、强度和频率来增强子宫收缩。研究激素调节子宫收缩性潜在机制的最具信息量的方法是在未经过酶处理以进行细胞分离或细胞培养条件的完整子宫肌层样本中记录对激素的[Ca(2+)]i反应。然而，由于收缩组织中出现的运动伪影，这种记录的时空分辨率受到限制。在这里，我们描述了我们新开发的运动校正算法在细胞水平上研究对照和催产素刺激的人子宫肌层切片中[Ca(2+)]i动力学的应用。我们提供的证据表明，催产素在完整子宫肌层内的单个肌细胞中诱导异步[Ca(2+)]i振荡，这与在培养细胞中观察到的振荡相似。这些振荡发生在同步动作电位驱动的[Ca(2+)]i瞬变之间，但似乎与收缩无关。此外，催产素触发的[Ca(2+)]i振荡在激素应用后30 - 50分钟内减弱，而动作电位诱导的[Ca(2+)]i瞬变仍然增强。我们得出结论，催产素诱导的[Ca(2+)]i振荡与子宫肌层收缩性的急性调节无关，但可能在长期调节过程中起作用，例如通过触发基因表达。
