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Int. J. Mol. Sci. 2018, 19(5), 1413; https://doi.org/10.3390/ijms19051413

Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium

1
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania
2
Faculty of Medical Engineering, University Politehnica of Bucharest, Gheorge Polizu Street 1-7, 011061 Bucharest, Romania
3
Department of Life and Environmental Physics, Horia Hulubei National Institute of Physics and Nuclear Engineering, Reactorului 30, P.O. Box MG-6, 077125 Magurele, Romania
4
Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 011061 Bucharest, Romania
5
Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
6
Alessandrescu-Rusescu National Institute of Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania
7
Cardiac Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China
8
Department of Obstetrics and Gynecology, Polizu Clinical Hospital, 011062 Bucharest, Romania
9
Life, Environmental and Earth Sciences Division, Research Institute of the University of Bucharest (ICUB), 91-95 Splaiul Independenţei, 050095 Bucharest, Romania
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 20 March 2018 / Revised: 14 April 2018 / Accepted: 2 May 2018 / Published: 9 May 2018
(This article belongs to the Special Issue Calcium Signaling in Human Health and Diseases)
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Abstract

Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1), estrogen receptors (ESR1, ESR2, GPR30), and nuclear receptor coactivator 3 (NCOA3). Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM) downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM) antagonized the effect of BAY K8644 (2.5 or 5 µM) in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant human uterine myometrium and their gene expression regulation by beta-estradiol in pregnant conditions. Further exploration of the calcium signaling in TCs and its modulation by estrogen hormones will contribute to the understanding of labor and pregnancy mechanisms and to the development of effective strategies to reduce the risk of premature birth. View Full-Text
Keywords: beta-estradiol; human uterine myometrium; telocytes; calcium signaling; voltage-gated calcium channels; estrogen receptors beta-estradiol; human uterine myometrium; telocytes; calcium signaling; voltage-gated calcium channels; estrogen receptors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Banciu, A.; Banciu, D.D.; Mustaciosu, C.C.; Radu, M.; Cretoiu, D.; Xiao, J.; Cretoiu, S.M.; Suciu, N.; Radu, B.M. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium. Int. J. Mol. Sci. 2018, 19, 1413.

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