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

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 (I-Ca) 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 alpha 1 subunit Ca(v)1.2. 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) I-Ca 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 alpha 1 subunit (Ca(v)1.2; alpha 1c) messenger RNA (mRNA) and protein expressions were unchanged. Among 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 2 alpha, beta 3, and beta 4 mRNA and protein expressions were not different between groups, protein expression of the beta 1 subunit (Ca-v beta 1) 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 Ca-v beta 1 subunit expression.