Contraction kinetics of isolated human myometrium during menstrual cycle and pregnancy
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Myometrial contraction frequency and force recovery kinetics, particularly in response to protein kinase C activation, vary significantly between the follicular phase, luteal phase, and pregnancy at term.
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Abstract
OBJECTIVE: To investigate the interaction between actin and myosin in the myometrium by studying the contraction kinetics of isolated samples of human myometrium. DESIGN: Experimental and observational cross-sectional study. SETTING: Eppendorf University Hospital, Hamburg. SAMPLES: Myometrium samples were taken from women in the follicular phase (n = 6) or luteal phase (n = 6) of the menstrual cycle and during pregnancy at term (n = 25). METHODS: The frequency, extent and rate of force development were determined in spontaneously active myometrial preparations. From a resting force of 2 mN, sustained tonic contractions were induced by K+-depolarisation (124 mM), or by protein kinase C activation (19 x 9 microM indolactam). The steady force was reversibly interrupted by rapid length changes (100 Hz sinus vibrations lasting 1 s, 5% of muscle length). Extent (steady plateau), as well as rate of force increase after cessation of vibrations, were derived from bi-exponential functions fitted to the time course of force recovery. RESULTS: Frequency of spontaneous contractions was higher in the follicular phase [mean (SD) 18 x 3 contractions/hour (1 x 0)] than in the luteal phase [13 x 4 contractions/hour (8 x 1)] or in pregnancy at term [8 x 8 contractions/hour (7 x 6)]. During indolactam treatment, steady force in pregnancy at term was significantly increased [8 x 8 mN (4 x 0)], compared with the follicular phase [3 x 7 mN (0 x 9)]. Force recovery was distinctly slower in pregnancy at term during indolactam treatment [time constant 99 x 2 s (57 x 9); P < 0 x 005] than during K+-depolarisation [time constant 29 x 1 s (5 x 9)], whereas in the follicular phase the rate of force recovery was faster with indolactam [16 x 8 s (7 x 1)] than with K+ depolarisation [24 x 4 s (5 x 9); P < 0 x 005]. CONCLUSIONS: The responses of human myometrium to contraction stimuli differ according to the reproductive state. Membrane depolarisation causes similar responses in all myometrial strips. In contrast, near term stimulation of protein kinase C generates a large tonic force and slow contraction kinetics, whereas early in the menstrual cycle contraction kinetics are fast.
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