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

Abstract

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 F2α (PGF). 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). 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. 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. 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. 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.

Role of T-type Ca2+ Channels in the Spontaneous Phasic Contraction of Pregnant Rat Uterine Smooth Muscle

“…The results are consistent with a previous study that mibefradil inhibited the frequency as well as amplitude of uterine contractility (Asokan et al, 2002 ]i and force. According to the previous report, high K ＋ -induced contraction is due to Ca 2＋ influx through L-type Ca 2＋ channel by membrane depolarization (Shmigol et al, 1998;Coleman et al, 2000). In the present study, we also showed that 1 μM nifedipine, L-type Ca 2＋ channel blocker, completely inhibited high K ＋ -induced contraction.…”

Hormonal signaling and signal pathway crosstalk in the control of myometrial calcium dynamics

“…Oxytocin also elicited a long-lasting nonselective cation current consistent with SRCE in late pregnant rat myometrium [60]. Furthermore, the sustained phase of [Ca 2+ ] i elevation after PGF2α-induced contractions in pregnant guinea pig myometrium was not affected by nifedipine [52], consistent with SRCE.…”

“…In pregnant guinea pig myometrium, PGF2α stimulated sustained depolarization and biphasic increases in [Ca 2+ ] i at mid to late-pregnancy; nifedipine inhibited most of the former but only some of the latter [52]. Verapamil, an L-type channel inhibitor, significantly reduced PGF2α-stimulated PI turnover in late pregnant human myometrium [2,47].…”

Electrical slow waves in the mouse oviduct are dependent on extracellular and intracellular calcium sources

“…Nifedipine produced a 13-mV depolarization in membrane potential and caused cessation of slow waves. This effect is similar to that reported previously in the guinea pig myometrium where nifedipine produced an identical 13-mV depolarization and abolished spontaneous electrical activity (8). In uterine muscles, depolarization caused by nifedipine was thought to be due to suppression of K v or K Ca channels.…”