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

Abstract

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.