Oxytocin-induced Ca2+ responses in human myometrial cells

Complex spatiotemporal changes in intracellular Ca2+ were monitored in an i mmortalized human myometrial cell line (PHM1-41) and first-passage human my ometrial cells after oxytocin stimulation (1.0-1000 nM). Laser cytometry re vealed intracellular Ca2+ oscillations in both culture systems starting at 1.0 nM, which were followed by repetitive Ca2+ transients by 10-15 min that lasted for at least 90 min. The amplitude of the initial Ca2+ spike was do se dependent, while the frequency of Ca2+ oscillations identified by Fast F ourier Transform (FFT) tended to increase with dose. Removal of oxytocin re sulted in termination of oscillations. Analysis of the sources of the Ca2involved in oscillations indicated that the major contribution to oscillati on frequencies of less than or equal to 6 mHz in cells was from the inosito l 1,4,5-trisphosphate-sensitive pool, accounting for about 60% of the frequ encies. Most of the remaining frequencies were attributable to extracellula r Ca2+, which presumably comes from plasma membrane channels other than L-t ype channels. When oscillation frequencies exceeded 6 mHz, a significant co ntribution from a ryanodine-sensitive Ca2+ pool was detected. Eight-bromo-c AMP suppressed both the initial Ca2+ spike and the long-term oscillations. Prostaglandin E-1 and E-2 caused a significant increase in the frequency of oxytocin-induced Ca2+ oscillations. FFT analysis may be of considerable va lue for study of the mechanisms of rhythmic Ca2+ transients and their funct ion in myometrial cells, as well as the mechanisms by which uterotonins and tocolytic agents impact myometrial Ca2+ regulation.