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首页> 外文期刊>Brain research >Release of GABA from sensory neurons transduced with a GAD67-expressing vector occurs by non-vesicular mechanisms.
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Release of GABA from sensory neurons transduced with a GAD67-expressing vector occurs by non-vesicular mechanisms.

机译：GABA从表达GAD67的载体转导的感觉神经元中释放是通过非水泡机制发生的。

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摘要

We have demonstrated that dorsal root ganglion neurons transduced with a recombinant replication-defective herpes simplex virus vector coding for glutamic acid decarboxylase (QHGAD67) release GABA to produce an analgesic effect in rodent models of pain. In this study, we examined the mechanism of transgene-mediated GABA release from dorsal root ganglion neurons in vitro and in vivo. Release of GABA from dorsal root ganglion neurons transduced with QHGAD67 was not increased by membrane depolarization induced by 60 mM extracellular K+ nor reduced by the removal of Ca2+ from the medium. Release of GABA from transduced dorsal root ganglion neurons was, however, blocked in a dose-dependent manner by NO-711, a selective inhibitor of the GABA transporter-1. The amount of GABA released from a spinal cord slice preparation, prepared from animals transduced by subcutaneous inoculation of QHGAD67 in the hind paws, was substantially increased compared to animals transduced with control vector Q0ZHG or normal animals, but the amount of GABA released was not changed by stimulation of the dorsal roots at either low (0.1 mA, 0.5-ms duration) or high (10 mA, 0.5-ms duration) intensity. We conclude that QHGAD67-mediated GABA release from dorsal root ganglion neurons is non-vesicular, independent of electrical depolarization, and that this efflux is mediated through reversal of the GABA transporter.
机译：我们已经证明，用编码谷氨酸脱羧酶（QHGAD67）的重组复制缺陷型单纯疱疹病毒载体转导的背根神经节神经元释放GABA在啮齿类动物疼痛模型中产生镇痛作用。在这项研究中，我们在体外和体内研究了转基因介导的GABA从背根神经节神经元释放的机制。从QHGAD67转导的背根神经节神经元释放GABA不会因60 mM细胞外K +引起的膜去极化而增加，也不会因从培养基中去除Ca2 +而减少。然而，GABA从转导的背根神经节神经元中的释放以剂量依赖性方式被GABA转运蛋白1的选择性抑制剂NO-711阻断。与通过对照载体Q0ZHG或正常动物转导的动物相比，从通过皮下接种QHGAD67在后爪中转导的动物制备的脊髓切片制剂释放的GABA的量显着增加，但是释放的GABA的量没有改变通过以低强度（0.1 mA，持续时间0.5毫秒）或高强度（10 mA，0.5毫秒持续时间）刺激背根。我们得出结论，QHGAD67介导的背根神经节神经元释放的GABA是非囊泡的，独立于电去极化，并且这种流出是通过GABA转运蛋白的逆转介导的。

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