Relaxant Effect of Cyppa In Vitro and Expression Analysis of SK3 Splice Variants in the Myometrium of Pregnant and Non-Pregnant WomenRosenbaum ST1,2*, Svalo J2, Larsen T1, Joergensen J1 and Bouchelouche P2
- *Corresponding Author:
- Sofia T Rosenbaum
Department of Gynecology and Obstetrics
Holbaek Hospital, 60 Smedelundsgade
4300 Holbaek, Denmark
Tel: 0045 4732 5509
E-mail: [email protected]
Received date: August 22, 2013; Accepted date: September 17, 2013; Published date: September 20, 2013
Citation: Rosenbaum ST, Svalo J, Larsen T, Joergensen J, Bouchelouche P (2013) Relaxant Effect of Cyppa In Vitro and Expression Analysis of SK3 Splice Variants in the Myometrium of Pregnant and Non-Pregnant Women. Gynecol Obstet 3:171. doi: 10.4172/2161-0932.1000171
Copyright: © 2013 Rosenbaum ST, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background and objective: We have recently shown an overall down-regulation of SK3 channels in pregnant human myometrium compared to non-pregnant myometrium. The aim of this study was to investigate whether SK3 splice variants are involved in the down-regulation of SK3 channels. We also tested whether SK channels are implicated in myometrial contractility using CyPPA, a novel and selective SK2 and SK3 channel activator.
Study design: We evaluated the expression of SK3 splice variants at mRNA level by qRT-PCR in myometrium from pregnant (n=11) and non-pregnant (n=11) women. Isometric tension recordings were performed to assess human myometrial contractility on biopsies obtained at elective caesarean section at term (n=6) and from hysterectomy (n=6). We investigated the effects of CyPPA (0.1-60 μM) on spontaneous contractions.
Results: The relative quantity of SK3 variant 3 did not differ between myometrium from pregnant and non-pregnant women (P=0.332). Variant 2 was not found present at detectable amounts. In contrast, SK3 variant 1 showed a 3-fold down-regulation in pregnant compared to non-pregnant myometrium (P=0.002).
CyPPA depressed spontaneous phasic contractions in human myometrial strips of both non-pregnant and pregnant origin. It took place in a concentration-dependent manner (where pIC50 = 5.02 ± 0.08 and 5.16 ± 0.15, respectively, and P>0.05), with contractions being abolished at 60 μM CyPPA.
Conclusions: We have been successful in demonstrating the presence of SK3 splice variants in human myometrium, for the first time. We also show that SK3 variant 1 is down-regulated in pregnant myometrium, and that it may be responsible for the overall down-regulation of SK3 channels observed in pregnant, as compared to nonpregnant, human myometrium. CyPPA exerts a potent relaxant effect on human myometrial tissue. This suggests that SK3 channels may be a new pharmacological target for the development of tocolytica.