[CA2+](I) SIGNALING IN PREGNANT HUMAN MYOMETRIUM

The purpose of the present study was to determine the changes in intra cellular ionized calcium concentration ([Ca2+](i)) or [Ca2+](i) sensit ivity accompanying spontaneous and agonist-induced contraction of huma n myometrium at term pregnancy, as well as to quantify the response to three prototypical agonists: 1) oxytocin, 2) vasopressin, and 3) phen ylephrine. Uterine biopsies were obtained at the time of cesarean sect ion 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. Concentr ation-response relationships were determined with respect to isometric force development in the presence of the agonist. [Ca2+](i)-force rel ationships were determined with respect to spontaneous phasic contract ions, as well as agonist-induced phasic and tonic contractions. The re sults 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 maint ain high [Ca2+](i) levels for prolonged periods of time. In addition, calcium-independent mechanisms of regulation were suggested by the rel atively minor calcium sensitizing action of oxytocin and the observati on that relaxation of tonic contractions preceded the fall in [Ca2+](i ) levels.