Single-cell mechanics and calcium signalling in organotypic slices of human myometrium

JOURNAL OF BIOMECHANICS

卷:48

Article

Loftus, Fiona C.^1,2,3  Richardson, Magnus J. E.¹  Shmygol, Anatoly² 

[1] Univ Warwick, Warwick Syst Biol Ctr, Coventry CV2 2DX, W Midlands, England

[2] Univ Warwick, Warwick Med Sch, Div Translat & Syst Med, Coventry CV2 2DX, W Midlands, England

[3] Univ Warwick, Warwick Syst Biol Doctoral Training Ctr, Coventry CV2 2DX, W Midlands, England

关键词: Myometrium;    Calcium signalling;    Motion artifacts correction;    Oxytocin;   

DOI  :  10.1016/j.jbiomech.2015.01.046

来源: Elsevier

【 摘 要 】

Elucidation of cellular mechanisms regulating myometrial contractility is crucial for improvement in management of many obstetric abnormalities, such as premature delivery, uterine dystocia and postpartum haemorrhage. Myometrial contractions are triggered by periodic synchronous rises in intracellular calcium concentration ([Ca2+](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 [Ca2+](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 spatiotemporal 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 [Ca2+](i) dynamics in control and oxytocin stimulated slices of human myometrium on a cellular level. We present evidence that oxytocin induces asynchronous [Ca2+](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 [Ca2+](i) transients but appear to be unrelated to contractions. Furthermore, the oxytocin-triggered [Ca2+](i) oscillations wane within 30-50 min of hormone application, while the action potential induced [Ca2+](i) transients remain augmented. We conclude that oxytocin-induced [Ca2+](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. (C) 2015 The Authors. Published by Elsevier Ltd.

【 授权许可】

Free