Modification of Women Uterine Contractile Activities by Chronic T4-Treatment are Related to Changes in Ca2+ and K+ Conductance: Clinical to Bench Side Analysis

Abstract

Significant time course modifications of uterine contractile activities were observed in Levothyroxine-treated pregnant women, including increased amplitude and duration of phasic contractions in vitro. This study aimed to investigate the involvement of Ca2+ and K+ conductance in controlling repetitive contractile activities in an in vitro model of human uterine strips. Thus, the ability of Ba2+ to modulate Ca2+ and K+ conductance was used to alter the pattern of control uterine contractile activities. Uterine biopsies were performed from consenting women undergoing elective caesarean sections at term (N=12). Isometric tension measurements were performed in vitro on fresh human myometrial strips in isolated organ baths. After a 2 h equilibration period, the effects of Iberiotoxin (IbTx), a selective BKca blocker, Ba2+ and Lemakalim, a potassium channel opener were assessed on spontaneous uterine contractile activities. Uterine contractions were quantified by calculating the amplitude, the duration, the frequency and the area under the curve over 20-min periods. Our data demonstrated a significant increase in both amplitude and duration of phasic contractions following addition of 2 mM Ba2+, partially mimicking the result obtained upon T4-treatment during pregnancy. Addition of 100 nM IbTx, slightly increased these parameters, similarly to acute T3 treatments (p<0.05). Use of 1 μM Lemakalim efficiently abolished in vitro uterine contractions. Following 2 mM Ba2+, cumulative addition of Lemakalim produced relaxing effects (p<0.05). Moreover, in the presence of a hypokalemic physiological solution containing 1 mM KCl (as opposed to 4.7 mM) a tocolytic effect was quantified, an effect likely related to enhanced K+ conductance. Our data suggestthat in uterine strips, modifications of GK+ could alter the contractile pattern, which would explain the abnormal time course of uterine repetitive contractions.