Tharp Darla L, Ivey Jan R, Shaw Rebecca L, Bowles Douglas K
From the 1Department of Biomedical Sciences, 2Dalton Cardiovascular Research Center, and 3Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO.
Menopause. 2014 Jun;21(6):661-8. doi: 10.1097/GME.0000000000000087.
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.
Sexually mature female swine were obtained from a breeder and either left intact (intact female [IF]; n = 5) or ovariectomized (n = 6).
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 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.
Endogenous female hormones inhibit L-type Ca channel activity in coronary SMCs potentially via the up-regulation of Cavβ1 subunit expression.
已证实性激素状态在离子通道活性调节中发挥作用。我们之前证明，与雌性猪相比，雄性猪冠状动脉平滑肌细胞（SMC）中的L型钙通道电流（ICa）增加。在雄性猪中，内源性睾酮通过增强孔形成α1亚基Cav1.2的表达来增加SMC中的ICa。相反，性激素在雌性猪中的作用此前尚未得到研究。因此，本研究的目的是确定卵巢切除术（OVX）对雌性尤卡坦小型猪L型钙通道活性和表达的影响。
从饲养者处获得性成熟的雌性猪，要么保持完整（完整雌性[IF]；n = 5），要么进行卵巢切除（n = 6）。
OVX增加了对去极化诱导收缩的敏感性。相应地，与IF组（-4.5 [0.3] pA/pF）相比，OVX组的平均（SEM）ICa增强（-9.5 [0.6] pA/pF），尽管L型钙通道α1亚基（Cav1.2；α1c）信使核糖核酸（mRNA）和蛋白质表达没有变化。在L型钙通道β亚基中，β1（188 [31]）和β2a（561 [79]）的mRNA表达水平（靶标/18S）高于β3（9 [1]）和β4（2 [0.1]）。尽管β2a、β3和β4的mRNA和蛋白质表达在组间没有差异，但与IF组相比，OVX组中β1亚基（Cavβ1）的蛋白质表达降低。
内源性雌性激素可能通过上调Cavβ1亚基表达来抑制冠状动脉SMC中的L型钙通道活性。
