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

Objective: This study was carried out to examine the effect of functional modification of Caactivated 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: Ca-activated Cl currents play a significant role in the spontaneous and oxytocininduced myometrial activity. Ca-activated Cl conductance could hence be a potential target for the pharmacological control of uterine activity.