Effect of functional modulation of Ca2+-activated Cl- currents on gravid rat myometrial activity

OBJECTIVE: This study was carried out to examine the effect of functional modification of Ca²⁺-activated Cl^- currents on contractile activities of isolated gravid rat myometrium.
MATERIALS AND METHODS: Spontaneous rhythmic and oxytocin-induced contractile activities of gravid rat myometrium in the presence and absence of Cl^- (in the bathing medium) were studied in a tissue bath system. The effects of niflumic acid (a Cl^- channel blocker) on spontaneous and oxytocin-induced contractile activities were also delineated.
RESULTS: Replacement of Cl^--containing Tyrode solution with Cl^--free medium caused transient increase in myometrial contractile tone for about 15 min (possibly due to rapid efflux of Cl^-) after which gradual failure of the spontaneous contractions led to myometrial quiescence within 1 h. Normal spontaneous contractions returned after replacing Cl^--free medium with Tyrode solution. In Cl^--free medium, oxytocin-induced contractions of the myometrium were significantly reduced by 44 ± 9%. Niflumic acid (30 µM) caused an increase in myometrial contractile tone for about 10 min followed by time-dependent inhibition of spontaneous contractions of the rat myometrium. Moreover, prior addition of 30 µM of niflumic acid to the tissue baths (for 30 min) caused 74 ± 5% reduction of oxytocin-induced contractions of the myometrial strips.
CONCLUSION: Ca²⁺-activated Cl^- currents play a significant role in the spontaneous and oxytocin-induced myometrial activity. Ca²⁺-activated Cl^- conductance could hence be a potential target for the pharmacological control of uterine activity.