GABAA AND GABAB RECEPTORS HAVE OPPOSITE EFFECTS ON SYNAPTIC GLUTAMATE RELEASE ON THE NUCLEUS TRACTUS SOLITARII NEURONS
GABAA AND GABAB RECEPTORS HAVE OPPOSITE EFFECTS ON SYNAPTIC GLUTAMATE RELEASE ON THE NUCLEUS TRACTUS SOLITARII NEURONS
复制标题
DOI：
10.1016/j.neuroscience.2012.02.025
复制
发表时间：
2012-05-03
期刊：
影响因子：
3.3
通讯作者：
Jin, Y. -H.
中科院分区：
文献类型：
--
作者：
Kang, Y. -H.;Sun, B.;Jin, Y. -H.
颅内脏传入神经通过释放兴奋性神经递质谷氨酸将内脏器官的信息传递到孤束核。各种内源性调节剂通过改变NTS中的谷氨酸能反应来影响自主反射反应。虽然GABA(A)和GABA(B)受体在谷氨酸末端的表达是已知的，但它们对谷氨酸释放的功能贡献却知之甚少。在这里，我们使用机械分离的NTS神经元来研究突触前GABA(A)和GABA(B)受体调节谷氨酸能兴奋性突触后电流（EPSCs）的机制。在不含GABA受体拮抗剂的情况下，采用氯离子平衡电位（-49 mV）箝位法分离EPSC。在所有神经元中，GABA(A)激动剂muscimol （1 μ M和10 μ M）增加EPSC频率（分别为对照组的284.1+/-57%和278.4+/-87%），而GABA(B)激动剂巴氯芬（10 μ M）降低EPSC频率（43+/-8%）。GABA(A)拮抗剂gabazine （18 μ M）降低了50%的神经元EPSC频率，而GABA(B)拮抗剂CGP （5 μ M）增加了36%的神经元EPSC频率。外用GABA（1和30 μ M）促进EPSC频率。GABA(A)受体介导的谷氨酸释放的促进作用被Na+- k +- cl -共转运蛋白1型拮抗剂或Na+和Ca2+通道抑制剂阻断，表明GABA(A)突触前去极化。因此，强直释放的GABA激活GABA(A)和GABA(B)受体来调节谷氨酸的释放。这些发现提供了外周内脏传入信号在NTS中的异突触gaba -谷氨酸整合的细胞机制。(c) 2012 ibro。Elsevier Ltd.出版。版权所有。
Cranial visceral afferent nerve transfers information about visceral organs to nucleus tractus solitarii (NTS) by releasing the excitatory neurotransmitter glutamate. Various endogenous modulators affect autonomic reflex responses by changing glutamatergic responses in the NTS. Although the expression of GABA(A) and GABA(B) receptors in glutamatergic terminals is known, their functional contribution on glutamate release is poorly characterized. Here, we used mechanically isolated NTS neurons to examine the mechanisms by which presynaptic GABA(A) and GABA(B) receptors modulate glutamatergic excitatory postsynaptic currents (EPSCs). EPSC were isolated by clamping voltage at equilibrium potential for chloride (-49 mV) without any GABA receptors antagonists. In all neurons, GABA(A) agonist, muscimol (1 and 10 mu M), increased EPSC frequency (284.1+/-57% and 278.4+/-87% of control, respectively), but the GABA(B) agonist, baclofen (10 mu M), decreased EPSC frequency (43+/-8% of control). The GABA(A) antagonist, gabazine (18 mu M), decreased EPSC frequency in 50% of tested neurons, whereas GABA(B) antagonist, CGP (5 mu M), increased the EPSC frequency in 36% of tested neurons. External application of GABA (1 and 30 mu M) facilitating the EPSC frequency. The facilitation of the GABA(A) receptor-mediated release of glutamate was blocked by Na+-K+-Cl- cotransporter type 1 antagonist or Na+ and Ca2+ channel inhibitors indicating GABA(A) presynaptic depolarization. Thus, tonically released GABA activates GABA(A) and GABA(B) receptors to modulate the release of glutamate. These findings provide cellular mechanisms of heterosynaptic GABA-glutamate integration of peripheral visceral afferent signals in the NTS. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.