The role of cellular coupling in the spontaneous generation of electrical activity in uterine tissue

PLoS One. 2015 Mar 20;10(3):e0118443. doi: 10.1371/journal.pone.0118443. eCollection 2015.

Abstract

The spontaneous emergence of contraction-inducing electrical activity in the uterus at the beginning of labor remains poorly understood, partly due to the seemingly contradictory observation that isolated uterine cells are not spontaneously active. It is known, however, that the expression of gap junctions increases dramatically in the approach to parturition, by more than one order of magnitude, which results in a significant increase in inter-cellular electrical coupling. In this paper, we build upon previous studies of the activity of electrically excitable smooth muscle cells (myocytes) and investigate the mechanism through which the coupling of these cells to electrically passive cells results in the generation of spontaneous activity in the uterus. Using a recently developed, realistic model of uterine muscle cell dynamics, we investigate a system consisting of a myocyte coupled to passive cells. We then extend our analysis to a simple two-dimensional lattice model of the tissue, with each myocyte being coupled to its neighbors, as well as to a random number of passive cells. We observe that different dynamical regimes can be observed over a range of gap junction conductances: at low coupling strength, corresponding to values measured long before delivery, the activity is confined to cell clusters, while the activity for high coupling, compatible with values measured shortly before delivery, may spread across the entire tissue. Additionally, we find that the system supports the spontaneous generation of spiral wave activity. Our results are both qualitatively and quantitatively consistent with observations from in vitro experiments. In particular, we demonstrate that the increase in inter-cellular electrical coupling observed experimentally strongly facilitates the appearance of spontaneous action potentials that may eventually lead to parturition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Electrophysiological Phenomena*
  • Female
  • Models, Biological
  • Muscle Cells / physiology
  • Myometrium / physiology*
  • Rats
  • Time Factors

Grants and funding

JX is supported by the Chinese National Science Foundation (11405145). RS, SNM and SS received funding from their institution, the Institute of Mathematical Sciences in Chennai. NBG and AP received funding from their institution, the Ecole Normale Supérieure de Lyon and CNRS. AP received support from the Humboldt foundation. Computer time on the “Annapurna” supercomputer was provided by the Institute for Mathematical Science in Chennai. Collaborative work was funded by the JoriSS exchange program from ENS Lyon, and by the Indo-French Center for Applied Mathematics program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.