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doi: 10.1097/GME.0b013e3182a7c05a
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Ovariectomy increases L-type calcium channel activity in porcine coronary smooth muscle.

Tharp, Darla L. PhD; Ivey, Jan R.; Shaw, Rebecca L.; Bowles, Douglas K. PhD

Published Ahead-of-Print
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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 coronary smooth muscle cells (SMCs) of male swine compared with female swine. In male swine, endogenous testosterone increases ICa in SMCs through enhanced expression of the pore-forming [alpha]1 subunit Cav1.2. Conversely, the role of sex hormones in female swine has not been previously investigated. Therefore, the purpose of the current study was to determine the effect of ovariectomy on L-type Ca2+ channel activity and expression in female Yucatan miniature swine.

Methods: Sexually mature female swine were obtained from a breeder and randomly assigned to intact female (IF; n = 5) and ovariectomized (OVX; n = 6) groups.

Results: Sensitivity to depolarization-induced contractions was increased by ovariectomy. Accordingly, L-type ICa was enhanced in OVX (-9.5 [0.6] pA/pF) versus IF (-4.5 [0.3] pA/pF) swine, although L-type Ca2+ channel [alpha]1 subunit (Cav1.2; [alpha]1c) messenger RNA (mRNA) and protein expressions were unchanged. Of the L-type Ca2+ channel [beta] subunits, [beta]1 (188 [31]) and [beta]2a (561 [79]) had higher mRNA expression levels (target/18S) than [beta]3 (9 [1]) and [beta]4 (2 [0.1]). Although [beta]2a, [beta]3, and [beta]4 mRNA and protein expressions were not different between groups, protein expression of the [beta]1 subunit (Cav[beta]1) was decreased in OVX swine compared with IF swine.

Conclusions: Endogenous female hormones inhibit L-type Ca2+ channel activity in coronary SMCs potentially via the up-regulation of Cav[beta]1 subunit expression.

(C) 2015 by The North American Menopause Society.


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