Ovariectomy increases L-type Ca(2+) channel activity in porcine coronary smooth muscle.

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 Ca 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 Ca 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 Ca channel α1 subunit (Cav1.2; α1c) messenger RNA (mRNA) and protein expressions were unchanged.Among the L-type Ca channel ß subunits, ß1 (188 [31]) and ß2a (561 [79]) had higher mRNA expression levels (target/18S) than ß3 (9 [1]) and ß4 (2 [0.1]). Although ß2a, ß3, and ß4 mRNA and protein expressions were not different between groups, protein expression of the ß1 subunit (Cavß1) was decreased in the OVX group compared with the IF group. CONCLUSIONS: Endogenous female hormones inhibit L-type Ca channel activity in coronary SMCs potentially via the up-regulation of Cavß1 subunit expression.