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Ovariectomy increases L-type Ca2+ channel activity in porcine coronary smooth muscle

Tharp, Darla L. PhD1; Ivey, Jan R.1; Shaw, Rebecca L.1; Bowles, Douglas K. PhD1,2,3

Menopause:
doi: 10.1097/GME.0000000000000087
Original Articles
Abstract

Objective: Sex hormone status has been demonstrated to play a role in the regulation of ion channel activity. We previously demonstrated increased L-type Ca2+ channel current (ICa) in the coronary smooth muscle cells (SMCs) of male swine compared with female swine. In male swine, endogenous testosterone increases ICa in SMCs by enhanced expression of the pore-forming α1 subunit Cav1.2. Conversely, the role of sex hormones in female swine has not previously been investigated. Therefore, the purpose of the current study was to determine the effect of ovariectomy (OVX) on L-type Ca2+ channel activity and expression in female Yucatan miniature swine.

Methods: Sexually mature female swine were obtained from a breeder and either left intact (intact female [IF]; n = 5) or ovariectomized (n = 6).

Results: Sensitivity to depolarization-induced contractions was increased by OVX. Accordingly, mean (SEM) ICa was enhanced in the OVX group (−9.5 [0.6] pA/pF) compared with the IF group (−4.5 [0.3] pA/pF), although L-type Ca2+ channel α1 subunit (Cav1.2; α1c) messenger RNA (mRNA) and protein expressions were unchanged.

Among the L-type Ca2+ channel β subunits, β1 (188 [31]) and β2a (561 [79]) had higher mRNA expression levels (target/18S) than β3 (9 [1]) and β4 (2 [0.1]). Although β2a, β3, and β4 mRNA and protein expressions were not different between groups, protein expression of the β1 subunit (Cavβ1) was decreased in the OVX group compared with the IF group.

Conclusions: Endogenous female hormones inhibit L-type Ca2+ channel activity in coronary SMCs potentially via the up-regulation of Cavβ1 subunit expression.

Author Information

From the 1Department of Biomedical Sciences, 2Dalton Cardiovascular Research Center, and 3Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO.

Received May 23, 2013; revised and accepted August 1, 2013.

Funding/support: This project was funded by National Institutes of Health grant 5RO1HL071574 (to D.K.B.).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Douglas K. Bowles, PhD, E102 Veterinary Medicine, University of Missouri, 1600 East Rollins, Columbia, MO 65211. E-mail: BowlesD@missouri.edu

© 2014 by The North American Menopause Society.