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The spontaneous emergence of contraction-inducing electrical activity in theuterus at the beginning of labor remains poorly understood, partly due to theseemingly contradictory observation that isolated uterine cells are notspontaneously active. It is known, however, that the expression of gapjunctions increases dramatically in the approach to parturition, which resultsin a significant increase in inter-cellular electrical coupling. In this paper,we build upon previous studies of the activity of electrically excitable smoothmuscle cells (myocytes) and investigate the mechanism through which thecoupling of these cells to electrically passive cells results in the generationof spontaneous activity in the uterus. Using a recently developed, realisticmodel of uterine muscle cell dynamics, we investigate a system consisting of amyocyte coupled to passive cells. We then extend our analysis to a simpletwo-dimensional lattice model of the tissue, with each myocyte being coupled toits neighbors, as well as to a random number of passive cells. We observe thatdifferent dynamical regimes can be observed over a range of gap junctionconductances: at low coupling strength, the activity is confined to cellclusters, while the activity for high coupling may spread across the entiretissue. Additionally, we find that the system supports the spontaneousgeneration of spiral wave activity. Our results are both qualitatively andquantitatively consistent with observations from in vitro experiments. Inparticular, we demonstrate that an increase in inter-cellular electricalcoupling, for realistic parameter values, strongly facilitates the appearanceof spontaneous action potentials that may eventually lead to parturition.

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