UMMS Affiliation

Department of Microbiology and Physiological Systems; Program in Molecular Medicine

Publication Date

2019-06-07

Document Type

Article Postprint

Disciplines

Biochemistry | Cell Biology | Developmental Biology | Molecular Biology | Molecular Genetics

Abstract

Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance and parturition; thus identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitro functional and pharmacological approaches have produced controversial results regarding the presence and role of TMEM16A Ca2+-activated Cl- channels in myometrial cells. To unambiguously determine the function of this channel in these cells, we employed a genetic approach by using smooth muscle cell-specific TMEM16A deletion (i.e. TMEM16ASMKO) mice. We found that myometrial cells from TMEM16ASMKO mice generated the same pattern and magnitude in Ca2+ signals upon stimulation with KCl, oxytocin and PGF2alpha compared to the isogenic control myometrial cells. At the uterine tissue level, TMEM16A deletion also did not cause detectable changes in either spontaneous or agonist (i.e. KCl, oxytocin and PGF2alpha)-induced contractions. Moreover, in vivo the TMEM16ASMKO mice gave birth at full term with the same litter size as genetically identical control mice. Finally, TMEM16A immunostaining in both control and TMEM16ASMKO mice revealed that this protein was highly expressed in the endometrial stroma, but did not co-localize with a smooth muscle specific marker MYH11. Collectively, these results unequivocally demonstrate that TMEM16A does not serve as a pacemaking channel for spontaneous uterine contraction, neither does it function as a depolarizing channel for agonist-evoked uterine contraction. Yet these two functions could underlie the normal gestation length and litter size in the TMEM16ASMKO mice.

Keywords

Calcium, Ion channels, Myometrium, Transgenic/Knockout model, Uterus

Rights and Permissions

© The Author(s) 2019. This is a pre-copyedited, author-produced version of an article accepted for publication in Biology of Reproduction following peer review. Accepted manuscript posted after 12 months as allowed by the publisher's author rights policy at https://academic.oup.com/journals/pages/access_purchase/rights_and_permissions/self_archiving_policy_b.

DOI of Published Version

10.1093/biolre/ioz096

Source

Biol Reprod. 2019 Jun 7. pii: 5512587. doi: 10.1093/biolre/ioz096. Link to article on publisher's site

Journal/Book/Conference Title

Biology of reproduction

Related Resources

Link to Article in PubMed

PubMed ID

31175367

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