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 F2alpha (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 mid-pregnancy 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.