[Ca2+]i signaling in pregnant human myometrium

Abstract

The purpose of the present study was to determine the changes in intracellular ionized calcium concentration ([Ca2+]i) or [Ca2+]i sensitivity accompanying spontaneous and agonist-induced contraction of human myometrium at term pregnancy, as well as to quantify the response to three prototypical agonists: 1) oxytocin, 2) vasopressin, and 3) phenylephrine. Uterine biopsies were obtained at the time of cesarean section from patients who delivered at or near full-term gestation. These preparations were used to measure isometric force development and [Ca2+]i levels with the luminescent calcium indicator aequorin. Concentration-response relationships were determined with respect to isometric force development in the presence of the agonist. [Ca2+]i-force relationships were determined with respect to spontaneous phasic contractions, as well as agonist-induced phasic and tonic contractions. The results provide evidence that the phasic nature of term human myometrium is due to 1) the resting [Ca2+]i level being less than the calcium threshold for contractions and 2) the inability of the tissue to maintain high [Ca2+]i levels for prolonged periods of time. In addition, calcium-independent mechanisms of regulation were suggested by the relatively minor calcium sensitizing action of oxytocin and the observation that relaxation of tonic contractions preceded the fall in [Ca2+]i levels.

Mathematical model of excitation-contraction in a uterine smooth muscle cell

“…It was suggested that desensitization of MLCK by phosphorylation after the first second following initiation of contraction causes a decrease in the rate of MLC phosphorylation and force production. Similar findings were obtained when the steady-state and transient C Ca,i vs. force relationships were investigated in strips of human pregnant myometria during spontaneous and agonist-induced contractions (22). Experiments with strips of pregnant and nonpregnant human myometria also revealed that MLC phosphorylation during contraction was lower in pregnant compared with nonpregnant tissue, while the amount of generated stress per MLC phosphorylation level was higher in the pregnant myometrial tissue (29).…”

ERK1/2-mediated phosphorylation of myometrial caldesmon during pregnancy and labor

“…Strips were mounted vertically in 50-ml tissue baths, and tension was recorded with an isometric tension transducer (Grass Instrument Division, West Warwick, RI). Experiments were performed at 37°C as previously described (34). Preparations were allowed to equilibrate for 1 h before initiation of experiments.…”

Regulation of Human Myometrial Contractility During Pregnancy and Labour: Are Calcium Homeostatic Pathways Important?

“…It is clear, however, that the primary trigger for human myometrial contractions (spontaneous and agonist induced) is a rise in intracellular calcium (Szal et al 1994;Luckas et al 1999). The relative contribution of calcium entry and calcium release from intracellular stores to the rise in intracellular calcium, however, is uncertain and is the focus of ongoing studies in our laboratory and others.…”