CONTRACTILE ELEMENTS AND MYOSIN LIGHT-CHAIN PHOSPHORYLATION IN MYOMETRIAL TISSUE FROM NONPREGNANT AND PREGNANT-WOMEN

Smooth muscle contraction is initiated primarily by an increase in int racellular Ca2+, Ca2+-dependent activation of myosin light chain kinas e, and phosphorylation of myosin light chain. In this investigation, w e identified pregnancy-associated alterations in myosin light chain ph osphorylation, force of contraction, and content of contractile protei ns in human myometrium. Steady-state levels of myosin light chain phos phorylation and contractile stress were correlated positively in both tissues, but the myometrial strips from pregnant women developed more stress at any given level of myosin light chain phosphorylation. Durin g spontaneous contractions and during conditions that favor maximal ge neration of stress, the rate and extent of myosin light chain phosphor ylation were attenuated in myometrial strips from pregnant women. The content of myosin and actin per milligram of protein and per tissue cr oss-sectional area was similar between myometrium of nonpregnant and p regnant women. Although cell size was significantly increased in tissu es obtained from pregnant women, the amounts of contractile proteins p er cellular cross-sectional area were similar. In addition, myosin lig ht chain kinase and phosphatase activities were similar in the two tis sues. The content of caldesmon was significantly increased in myometri um of pregnant women, whereas that of calponin (a smooth muscle-specif ic protein associated with the thin filaments) was not different. We c onclude that adaptations of human myometrium during pregnancy include (a) cellular mechanisms that preclude the development of high levels o f myosin light chain phosphorylation during contraction and (b) an inc rease in the stress generating capacity for any given level of myosin light chain phosphorylation.