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

TL;DR

This study explores how increased cellular electrical coupling in uterine tissue leads to spontaneous electrical activity, which is crucial for initiating labor, by modeling interactions between excitable and passive cells.

Contribution

It introduces a realistic model showing how coupling of myocytes with passive cells can generate spontaneous activity, advancing understanding of labor initiation mechanisms.

Findings

Higher gap junction conductance promotes widespread tissue activity.

Spiral wave activity can spontaneously emerge in the tissue model.

Increased coupling facilitates spontaneous action potentials leading to labor.

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, 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, the activity is confined to cell clusters, while the activity for high coupling 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 an increase in inter-cellular electrical coupling, for realistic parameter values, strongly facilitates the appearance of spontaneous action potentials that may eventually lead to parturition.