Tissue-Level Signaling and Control of Uterine Contractility: The Action Potential—Calcium Wave Hypothesis

Abstract

This article describes the action potential—calcium wave hypothesis of uterine contractility. Two known mechanisms of intercellular tissue-level signaling are merged into a single hypothesis of organ-level signaling. This hypothesis provides a framework with which to link cellular physiology with organ function. The two mechanisms of tissue-level signaling considered are action potential propagation and intercellular calcium waves. A great body of literature exists regarding the electrical excitability of smooth muscle and myometrium. Despite this knowledge, it does not seem possible to reconcile the familiar uterine contraction profile with known paraneters of cellular physiology unless a second mechanism of intercellular communication is postulated. Intercellular calcium waves fit the requirements needed for the second mechanism: slow speed, ability to raise interacellular free calcium, and ability to signal over hundreds of micrometers. The premise of the action potential—calcium wave hypothesis is that action potentials propagate rapidly throughout the uterus, initiating intercellular calcium waves. As the intercellular calcium waves propagate slowly through the bundles, myocytes are recruited to participate in the contraction. This article reviews and summarizes the literature on calcium waves in human myometrium and presents evidence to support the combination of these mechanisms. Extension of the hypothesis suggests that the functional unit of the laboring human uterus is the smooth-muscle bundle, and that the frequency and strength of uterine contractions are separate but linked physiologic characteristic of labor.