Flufenamic acid modulates multiple currents in gonadotropin-releasing hormone neurons.
Flufenamic acid modulates multiple currents in gonadotropin-releasing hormone neurons.
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DOI：
10.1016/j.brainres.2010.07.047
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发表时间：
2010-09-24
期刊：
影响因子：
2.9
通讯作者：
Kuehl-Kovarik MC
中科院分区：
文献类型：
--
作者：
Wang Y;Kuehl-Kovarik MC
哺乳动物的繁殖依赖于促性腺激素释放激素 (GnRH) 的适当神经分泌，但 GnRH 分泌背后的内源性活性仍知之甚少。我们已经证明，在老年动物分离的 GnRH 神经元中，调节爆发活性的去极化后电位 (DAP) 降低。钙激活的非特异性阳离子 (CAN) 通道有助于其他脊椎动物神经分泌细胞中的 DAP。我们使用 CAN 通道阻滞剂氟芬那酸 (FFA) 来检查衰老过程中 CAN 通道对 GnRH 神经元中 DAP 的贡献。对年轻、中年和老年雌性小鼠的分离荧光 GnRH 神经元进行记录。氟芬那酸抑制自发活动，但显着增加中青年动物神经元的 DAP。 Apamin 没有显着增强 DAP，但确实降低了 FFA 的作用，这表明 DAP 增加的部分原因是阻断 apamin 敏感的 SK 通道。氟芬那酸增加了所有年龄段 DAP 下的电流 (IADP) 并降低了之前的快速外向电流 (IOUT)。这些当前的反应不受 apamin 的影响，但 TEA 引起了类似的变化。因此，可能通过 BK 通道介导的钾电流有助于快速 AHP 并似乎抵消了 DAP；该电流对 FFA 敏感，但对年龄不敏感。 FFA 对 DAP（而非 IADP）的影响在老年动物中减弱，这可能反映了与年龄相关的 apamin 敏感 SK 通道的调节。未来的研究将检测 GnRH 神经元衰老过程中 SK 通道的表达。
Reproduction in mammals is dependent upon the appropriate neurosecretion of gonadotropin-releasing hormone (GnRH), yet the endogenous generation of activity underlying GnRH secretion remains poorly understood. We have demonstrated that the depolarizing afterpotential (DAP), which modulates bursting activity, is reduced in isolated GnRH neurons from aged animals. Calcium-activated non-specific cation (CAN) channels contribute to the DAP in other vertebrate neurosecretory cells. We used the CAN channel blocker flufenamic acid (FFA) to examine the contribution of CAN channels to the DAP in GnRH neurons during aging. Recordings were performed on isolated fluorescent GnRH neurons from young, middle-aged and aged female mice. Flufenamic acid inhibited spontaneous activity, but significantly increased the DAP in neurons from young and middle-aged animals. Apamin did not significantly potentiate the DAP, but did reduce the effects of FFA, suggesting that the increased DAP is partially due to blockade of apamin-sensitive SK channels. Flufenamic acid increased the current underlying the DAP (IADP) and decreased the preceding fast outward current (IOUT) at all ages. These current responses were not affected by apamin, but TEA evoked similar changes. Thus, a potassium current, likely mediated through BK channels, contributes to the fast AHP and appears to offset the DAP; this current is sensitive to FFA, but insensitive to age. The effect of FFA on the DAP, but not IADP, is diminished in aged animals, possibly reflecting an age-related modulation of the apamin-sensitive SK channel. Future studies will examine the expression of SK channels during the aging process in GnRH neurons.
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