Characterization of the tissue‐level Ca²⁺ signals in spontaneously contracting human myometrium

Abstract

In the labouring uterus, millions of myocytes forming the complex geometrical structure of myometrium contract in synchrony to increase intrauterine pressure, dilate the cervix and eventually expel the foetus through the birth canal. The mechanisms underlying the precise coordination of contractions in human myometrium are not completely understood. In the present study, we have characterized the spatio-temporal properties of tissue-level [Ca 2+ ] i transients in thin slices of intact human myometrium. We found that the waveform of [Ca 2+ ] i transients and isotonic contractions recorded from thin slices was similar to the waveform of isometric contractions recorded from the larger strips in traditional organ bath experiments, suggesting that the spatio-temporal information obtained from thin slices is representative of the whole tissue. By comparing the time course of [Ca 2+ ] i transients in individual cells to that recorded from the bundles of myocytes we found that the majority of myocytes produce rapidly propagating long-lasting [Ca 2+ ] i transients accompanied by contractions. We also found a small number of cells showing desynchronized [Ca 2+ ] i oscillations that did not trigger contractions. The [Ca 2+ ] i oscillations in these cells were insensitive to nifedipine, but readily inhibited by the T-type Ca 2+ channel inhibitor NNC55-0396. In conclusion, our data suggest that the spread of [Ca 2+ ] i signals in human myometrium is achieved via propagation of long-lasting action potentials. The propagation was fast when action potentials propagated along bundles of myocytes and slower when propagating between the bundles of uterine myocytes.

Fine spatiotemporal activity in contracting myometrium revealed by motion‐corrected calcium imaging

“… 2009 ; Bru-Mercier et al . 2012 ). Previously, direct comparisons of calcium activity within multiple cells in a contracting tissue slice was made difficult by the associated motion of the imaged tissue.…”

“…Full details are provided in Bru-Mercier et al . ( 2012 ). Briefly, each biopsy specimen was trimmed into a strip, which was then ligatured at both ends before being stretched and fixed to the base of a stainless steel tissue holder.…”

“…In Bru-Mercier et al . ( 2012 ), the [Ca 2+ ] i transients of cells both within the same bundle of myocytes and between two bundles during contraction were compared. The [Ca 2+ ] i measurements in this study reflect the averages of calcium indicator fluorescence from both the cell and the neighbouring region of tissue.…”

Functional insights into modulation of BKCa channel activity to alter myometrial contractility

“…Uterine contraction is primarily mediated by rises in cytoplasmic Ca 2+ concentration and activation of Ca 2+ -calmodulin/myosin light chain kinase pathways (Wray, 1993; Bru-Mercier et al, 2012). The mechanisms that elicit increases in intracellular Ca 2+ levels and contraction in myometrial smooth muscle cells (MSMCs) include: (i) Ca 2+ influx through voltage-gated Ca 2+ channels, (ii) agonist (e.g., acetylcholine or ATP) binding to receptor-operated channels, and (iii) binding of agonists (e.g., oxytocin) to receptors that evoke Ca 2+ release from intracellular stores (Inoue et al, 1992; Wray, 1993; Sanborn, 2000).…”

Linking Myometrial Physiology to Intrauterine Pressure; How Tissue-Level Contractions Create Uterine Contractions of Labor

“…Several mathematical simulations of organ-level functioning have been published, including action potential propagation mechanisms alone [6] , [7] , calcium waves [8] , and a previous cellular automaton approach [9] . Each has significant limitations, including failure to predict uterine behavior across the spectrum of clinical function, or direct disagreement with subsequently published data [10] . These limitations seem to reveal a poor understanding of how the uterus communicates at the organ-level.…”