GABAA Receptors Mediate Excitation in Adult Rat GnRH Neurons1
GABAA Receptors Mediate Excitation in Adult Rat GnRH Neurons1
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DOI：
10.1095/biolreprod.108.074583
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发表时间：
2009-08
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影响因子：
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通讯作者：
Miho Watanabe;Y. Sakuma;Masakatsu Kato
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文献类型：
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作者：
Miho Watanabe;Y. Sakuma;Masakatsu Kato
摘要 促性腺激素释放激素（GnRH）神经元形成生殖中枢调节的最终共同通路。 γ-氨基丁酸 (GABA) 是成人大脑中主要的抑制性神经递质，长期以来一直被认为在 GnRH 神经元的调节中发挥着关键作用。最近，两组报告称 GABA 可使 GnRH 神经元去极化，但一组报告称 GABA 具有超极化作用。在本研究中，我们研究了 GABA 诱导的 GnRH 增强绿色荧光蛋白 (GnRH-EGFP) 大鼠 GnRH 神经元 [Ca2+]i 的变化，以证实 GABA 的去极化作用，并进一步检查 GABA 作用的发育和动情周期依赖性调节。 GABA 增加男女所有发育阶段 GnRH 神经元中的 [Ca2+]i。 GABA 还增加了在每个发情周期阶段下午准备的成年雌性 GnRH 神经元中的 [Ca2+]i。 [Ca2+]i 增加的神经元百分比在发情前期为 90%，在发情期间为 59%，在发情间期 I 为 84%，在发情间期 II 为 89%。然而，在成年雌性早上制备的 GnRH 神经元中，该百分比显着低于下午制备的 GnRH 神经元（发情期除外）。成年男性的这一比例也低于成年女性。 GABA 反应被蝇蕈醇模仿并被荷包牡丹碱阻断。此外，细胞外Ca2+的去除完全抑制了GABA的作用，布美他尼减弱了反应。这些结果表明，GABA 通过激活 GABAA 受体使 GnRH 神经元去极化，从而激活电压门控 Ca2+ 通道并促进 Ca2+ 内流。此外，对 GABA 的反应根据动情周期阶段、昼夜节律和性别进行调节。
Abstract Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA), the main inhibitory neurotransmitter in the adult brain, has long been implicated in playing key roles in the regulation of GnRH neurons. Two groups reported recently that GABA depolarizes GnRH neurons, although one group reported a hyperpolarizing action of GABA. In this study, we investigated the GABA-induced changes in [Ca2+]i of GnRH neurons from GnRH-enhanced green fluorescent protein (GnRH-EGFP) rats both to confirm the depolarizing action of GABA and to further examine the developmental and estrous cycle-dependent modulations of GABA action. GABA increased [Ca2+]i in GnRH neurons at all developmental stages of both sexes. GABA also increased [Ca2+]i in adult female GnRH neurons prepared in the afternoon at each estrous cycle stage. The percentages of neurons with increased [Ca2+]i were 90% in proestrus, 59% in estrus, 84% in diestrus I, and 89% in diestrus II. In GnRH neurons prepared from adult females in the morning, however, the percentage was significantly lower than in those prepared in the afternoon, except in estrus. The percentage was also lower in adult males than in adult females. GABA responses were mimicked by muscimol and blocked by bicuculline. In addition, removal of extracellular Ca2+ completely suppressed the GABA action, and bumetanide attenuated the response. These results indicate that GABA depolarizes GnRH neurons by activating GABAA receptors, thereby activating voltage-gated Ca2+ channels and facilitating Ca2+ influx. In addition, the response to GABA is modulated according to the estrous cycle stage, diurnal rhythm, and sex.