Myometrial contractility involves the precise regulation of many signalling events to achieve efficient delivery of the fetus at term. Numerous signalling molecules have been suggested to cluster in cholesterol-rich plasmalemmal invaginations, termed caveolae. These include G-protein coupled-receptors and, in uterine myocytes, down-stream effectors such as rhoA and rho-associated kinase (ROK), where interaction with caveolar structural proteins, caveolins, may occur (Gimpl et al. 2000; Lee et al. 2001). Caveolae have also been implicated in the homeostasis of subcellular Ca²⁺ dynamics (Isshiki et al. 1998; Lohn et al. 2000). Thus, we studied the effects of a cholesterol-depleting agent, methyl-β-cyclodextrin (MβC), upon myometrial contractility.

Myometria were obtained, following written informed consent according to local ethics committee guidelines, from non-labouring term women undergoing elective Caesarean section (gestation 37-41 weeks). Small myometrial strips were dissected and mounted in standard organ baths in HCO₃^–-buffered physiological salt solution (37 °C, 95 % air-5 % CO₂). The experiments were performed with parallel time controls.

Following stabilisation of spontaneous phasic contractions, a 5 min application of 10 nM oxytocin induced a 23 ± 5 % rise in peak phasic tone (P < 0.05, Wilcoxon’s non-parametric test; mean ± S.E.M.; n = 7). Spontaneous contractions were allowed to recover. Subsequently, a 30 min incubation in 20 mM MβC resulted in an increased frequency of phasic contractile events, and a 42 ± 16 % increase in basal tone, with no change in peak phasic tone. After a 60-120 min incubation, phasic contractions were abolished and basal tone remained elevated at 46 ± 18 % of peak amplitude pre-treatment. The ensuing application of 10 nM oxytocin, in the presence of 20 mM MβC, produced no further elevation of tone.

This study indicates that a cholesterol-depleting agent reduces spontaneous and oxytocin-induced contractions in human myometrium, with an increase in basal tone. Further studies are required to determine the role of caveolae in these alterations.