Electrical wave generation and spatial organization in uterine tissue.

Abstract

Healthy uterine function requires coordinated and spatially organized contractions over the menstrual cycle (oestrus in animals) and at term in pregnancy. The underlying mechanisms triggering and coordinating uterine contractions, without a distinct pacemaking region, are poorly understood. Potentially, gap-junction coupling between excitable smooth muscle cells themselves or between electrically passive cells (telocytes or fibroblasts) and excitable cells may be key. Here, we present a lattice-tissue model of coupled excitable and passive cells to investigate a potential mechanism of coordinated tissue contraction. Bifurcation analysis of cell pairs quantifies parameter windows exhibiting oscillatory behaviour. Within these windows, we demonstrate conditions when the magnitude and spatial distribution of coupling strengths generate electrical waves. Energy-based analysis of excitable cells provides quantification of intercellular energy differences cells required for spontaneous wave generation. Our model suggests passive cells must rest at a membrane voltage sufficiently higher than smooth muscle cells to trigger activity and that coupling between excitable and passive cells in spatially concentrated regions could influence the direction of tissue-wide electrical waves. This suggests that both the total number of gap junctions and their spatial expression may play a role in coordinating uterine contractility.