Calcium-activated potassium channels (BKCa) are thought to contribute to the suppression of myometrial contractility during pregnancy prior to labour onset (Khan et al. 2001). There is a paucity of data, however, concerning the precise effect of BKCa channel blockade on contractile activity in pregnant myometrium. The aim of this study was to determine the effect of three BKCa channel inhibitors on spontaneous contractile activity in myometrium from non-pregnant and pregnant rats.
Myometrial tissue was obtained from humanely killed Sprague-Dawley rats: virgin (n = 18), early pregnant (day 7, n = 12), mid-pregnant (day 14, n = 12) and late pregnant (day 21, n = 12). Tissue was dissected longitudinally and mounted in four organ baths attached to a tension transducer and a MacLab system. Spontaneous contractile activity developed during 1 h equilibration period. Spontaneous contractions were then recorded for 15 min (control period) followed by the cumulative addition of (i) paxilline (1 or 10 µM), (ii) iberiotoxin (1, 10, 50 or 100 nM) or (iii) penitrim A (1, 10, 50, 100 or 500 nM). Vehicle controls were also performed. Contraction interval, integral, duration, and mean integral tension were measured for each drug addition and expressed as a percentage of the control period. Analysis used generalised estimating equations to correct for repeated measurement on each tissue sample (Liang & Zieger, 1986). The main comparison (the effect of drug concentration compared to vehicle controls) was carried out using an interaction test, assuming any drug effect was proportional to the log of concentration, a value of P < 0.05 was considered significant. None of the three inhibitors of BKCa channels significantly augmented spontaneous contractile activity in myometrium from non-pregnant or pregnant rats when compared to vehicle controls.
It was expected that inhibition of BKCa channels would significantly enhance spontaneous myometrial contractility. However the inability of the three inhibitors tested to modulate contractility in myometrium from non-pregnant and pregnant rats suggest that BKCa channels do not play a major role in mediating uterine quiescence in the pregnant rat. It remains to be elucidated whether BKCa channels contribute more to the control of myometrial contractility when tissues are co-incubated with fetal membranes or stimulated with agonists.
This work was supported by Tommy’s, the baby charity.