Tissue-level signaling and control of uterine contractility: The action potential-calcium wave hypothesis

This article describes the action potential-calcium wave hypothesis of uter ine contractility. Two known mechanisms of intercellular tissue-level signa ling are merged into a single hypothesis of organ-level signaling. This hyp othesis provides a framework with which to link cellular physiology with or gan function. The two mechanisms of tissue-level signaling considered are a ction potential propagation and intercellular calcium waves. A great body o f literature exists regarding the electrical excitability of smooth muscle and myometrium. Despite this knowledge, it does not seem possible to reconc ile the familiar uterine contraction profile with known parameters of cellu lar 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 intracellular free calcium, and ability to signal over hundreds of micrometers. The premise of the act ion potential-calcium wave hypothesis is that action potentials propagate r apidly throughout the uterus, initiating intercellular calcium waves. As th e intercellular calcium waves propagate slowly through the bundles, myocyte s are recruited to participate in the contraction. This article reviews and summarizes the literature on calcium waves in human myometrium that the fu nctional unit of the laboring human uterus is mechanisms. Extension of the hypothesis suggests that the functional unit of the laboring human uterus i s the smooth-muscle bundle, and that the frequency and strength of uterine contractions are separate but linked physiologic characteristics of labor. Copyright (C) 2000 by the Society for Gynecologic Investigation.