Changes in the mechanisms involved in uterine contractions during pregnancy in guinea-pigs

1. The mechanisms involved in contraction in guinea-pig myometrium were compared at mid- and late pregnancy. Tension was recorded simultaneously with either membrane potential or cytoplasmic calcium ([Ca2+](i)) in strips exposed briefly to prostaglandin F-2 alpha (PGF). 2. PGF-induced increases in tension were underpinned by action potentials followed by sustained depolarization and biphasic increases in [Ca2+](i) at mid- (peak, 879 +/- 199 nM; sustained, 298 +/- 35 nM, n = 11) and late pregnancy (peak, 989 +/- 302 nM; sustained 178 +/- 33 nM, n = 8). 3. At mid- and late pregnancy, nifedipine (10(-6) M) reduced (a) the PGF-induced increase in tension to 84 and 35%, (b) the level attained during the depolarization by 2 and 12 mV and (c) the peak rise in [Ca2+](i) to 42 and 17%. The sustained rises in [Ca2+](i) were resistant to nifedipine. 4. In Ca2+-free solution (containing 1 mM EGTA), PGF elicited an increase in tension that was 26% of that in 2.5 mM Ca2+ and an increase in [Ca2+](i) (24% of the sustained level) at midpregnancy but no increase in tension or [Ca2+](i) at term. 5. At both stages of pregnancy, PGF decreased the level of [Ca2+](i) required to elicit increases in tension comparable to those evoked by high K-o(+). The slope of the tension-[Ca2+](i) curves were steeper in mid- than in late pregnancy. 6. In conclusion, at mid-pregnancy, the contractile response of the guinea-pig myometrium to PGF involves Ca2+ influx through L-type voltage-operated Ca2+ channels (VOCCs) and by receptor-operated mechanisms, release of Ca2+ from intracellular stores, and an increase in the sensitivity of the contractile apparatus to Ca2+. At term the situation is different: a modest increase in the sensitivity of the contractile apparatus to Ca2+ persists and there is a major reliance on Ca2+ influx through VOCCs.