17β-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats
17β-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats
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DOI：
10.1152/ajpcell.00059.2009
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发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Schild, John H.
中科院分区：
文献类型：
--
作者：
Qiao, Guo-Fen;Li, Bai-Yan;Schild, John H.
乔GF，李BY，陆永健，付扬，Schild JH. 17 β-雌二醇恢复卵巢切除大鼠中有髓鞘迷走神经传入神经的性二态亚群的兴奋性。美国生理学杂志细胞生理学297：C654-C664，2009年。首次发表于2009年7月1日; doi：10.1152/ajpcell.00059.2009。我们最近确定了一个有髓迷走神经传入亚群（Ah型）远比男性大鼠更普遍的女性，并表明这种差异延伸到功能特异性内脏感觉传入，压力感受器的主动脉弓。有髓AH型传入的兴奋性显着降低卵巢切除术（OVX）后。在这里，我们测试的假设，17 β-雌二醇可以选择性地恢复这些性别特异性迷走神经传入的兴奋性。采用膜片钳技术和电流钳技术，观察了急性应用17 β-雌二醇（17 β-E2）对正常和去卵巢成年大鼠迷走神经传入神经元（VGN）兴奋性的影响。在超过生理相关的17 β-雌二醇浓度为大鼠（1-10 nM）的有髓鞘AH型迷走神经传入的兴奋性恢复到放电频率与那些在完整的女性，虽然有一些有趣的差异有关的突发和持续模式的神经元放电。兴奋性的恢复发生在激素应用的3分钟内，并且是立体特异性的，因为1，000 nM 17 α-雌二醇不能改变兴奋性。此外，G蛋白偶联雌激素受体GPR 30与高选择性激动剂G-1的激活类似地恢复AH型传入的兴奋性。通过应用高亲和力雌激素受体配体ICI 182，780，17 β-雌二醇和G-1的有效性完全消除。与BSA缀合的17 β-雌二醇在恢复Ah-type VGN兴奋性方面的有效性与单独的17 β-雌二醇的70%相似。这些数据支持了我们的结论，OVX后有髓鞘AH型VGN神经元兴奋性的快速恢复的细胞机制，至少部分是通过膜结合的雌激素受体发生的。我们认为，在生理相关的17 β-雌二醇浓度的高频放电的恢复意味着这种独特的亚型的低阈值髓鞘迷走神经传入可能占一些性别相关的差异，内脏器官系统功能。性别差异在心血管和胃肠道功能和GPR 30在调制性别特异性髓鞘AH型迷走神经传入的潜在作用进行了讨论。
Qiao GF, Li BY, Lu YJ, Fu YL, Schild JH. 17 beta-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats. Am J Physiol Cell Physiol 297: C654-C664, 2009. First published July 1, 2009; doi:10.1152/ajpcell.00059.2009.-We recently identified a myelinated vagal afferent subpopulation (Ah type) far more prevalent in female than male rats and showed that this difference extends to functionally specific visceral sensory afferents, baroreceptors of the aortic arch. Excitability of myelinated Ah-type afferents is markedly reduced after ovariectomy (OVX). Here we tested the hypothesis that 17 beta-estradiol can selectively restore excitability of these sex-specific vagal afferents. Acutely isolated vagal afferent neurons (VGN) from intact and OVX adult female rats were used with patch-clamp technique and current-clamp protocols to assess the effect of acute application of 17 beta-estradiol on neuronal excitability. At over physiologically relevant 17 beta-estradiol concentrations for rat (1-10 nM) excitability of myelinated Ah-type vagal afferents is restored to discharge frequencies comparable to those in intact females, albeit with some interesting differences related to burst and sustained patterns of neuronal discharge. Restoration of excitability occurs within 3 min of hormone application and is stereo specific, because 1,000 nM 17 alpha-estradiol fails to alter excitability. Furthermore, activation of G protein-coupled estrogen receptor GPR30 with highly selective agonist G-1 similarly restores excitability of Ah-type afferents. The effectiveness of 17 beta-estradiol and G-1 is completely eliminated by application of high-affinity estrogen receptor ligand ICI182,780. 17 beta-Estradiol conjugated with BSA is similar to 70% as effective as 17 beta-estradiol alone in restoring Ah-type VGN excitability. These data support our conclusions that the cellular mechanisms leading to rapid restoration of neuronal excitability of myelinated Ah-type VGN after OVX occur, at least in part, via membrane-bound estrogen receptors. We contend that recovery of high-frequency discharge at physiologically relevant 17 beta-estradiol concentrations implies that this unique subtype of low-threshold myelinated vagal afferent may account for some of the sex-related differences in visceral organ system function. Sex differences in cardiovascular and gastrointestinal function and the potential role of GPR30 in modulation of sex-specific myelinated Ah-type vagal afferents are discussed.