Oxytocin is commonly used to induce or augment labor, but its mode of action is uncertain. To address the issue, isometric tension and the intracellular free Ca2+ concentration ([Ca2+]i) were simultaneously recorded from isolated strips of pregnant human myometrium loaded with fura 2. The changes in [Ca2+]i and tension during phasic contractions were indistinguishable in myometrium taken before or after the onset of labor, enabling samples to be pooled. Oxytocin (10 nM) had no effect on basal [Ca2+]i or tension, but it increased both the [Ca2+]i and the tension recorded during phasic contractions. Analysis of the [Ca2+]i-tension relationship revealed that during the falling (relaxation) phase of the contractile response, oxytocin increased the tension recorded at each [Ca2+]i. By manipulating extracellular Ca2+ during phasic contractions, it was possible to ensure that the [Ca2+]i signals were similar in the presence and absence of oxytocin, yet oxytocin still improved the [Ca2+]i-tension relationship. We conclude that 10 nM oxytocin increases the [Ca2+]i sensitivity of the contractile proteins only after a contraction has begun, possibly by causing inhibition of myosin light chain phosphatase.
