Enhancement of tonic and phasic GABAergic currents following nitric oxide synthase inhibition in hippocampal CA1 pyramidal neurons
Enhancement of tonic and phasic GABAergic currents following nitric oxide synthase inhibition in hippocampal CA1 pyramidal neurons
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DOI：
10.1016/j.neulet.2015.01.058
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发表时间：
2015-03-17
影响因子：
2.5
通讯作者：
Calvo, Daniel J.
中科院分区：
文献类型：
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作者：
Gasulla, Javier;Calvo, Daniel J.
一氧化氮（NO）通过不同的突触前和突触后机制参与海马突触可塑性，包括gaba能神经传递的调节。海马锥体神经元上的抑制性突触具有逆行NO信号传导的分子机制，但这些神经元中NO对GABA(A)Rs功能的调节及其作用机制尚未完全表征。本研究表明，一氧化氮合酶（NOS）抑制剂L-NAME对内源性NO生成的抑制会使CA1海马锥体神经元的强直和相位gaba能电流的大小显著且可逆地增加。使用全细胞膜片钳记录年轻成年小鼠急性海马切片，在L-NAME存在或不存在的情况下测量gaba诱发的氯电流。L-NAME诱导的强直性GABA反应增强对TTX不敏感，与NO供体DEA/NO共孵育后减弱。单独应用DEA/NO对强直性GABA反应无显著影响。L-NAME处理也增加了GABA-puffs引起的相gaba能电流的振幅。我们的研究结果表明，GABA(A)受体介导的CA1海马锥体神经元的强直和相位抑制程度受内源性NO产生的影响。2015爱思唯尔爱尔兰有限公司版权所有。
Nitric oxide (NO) is involved in synaptic plasticity in the hippocampus through different presynaptic and postsynaptic mechanisms that include the modulation of the GABAergic neurotransmission. Inhibitory synapses on hippocampal pyramidal neurons are known to possess the molecular machinery for retrograde NO-signaling, but the modulation of GABA(A)Rs function by NO in these neurons and the mechanisms of action involved have not been fully characterized. Here we show that suppression of the endogenous NO generation by the nitric oxide synthase (NOS) inhibitor L-NAME produces significant and reversible increases in the magnitude of both tonic and phasic GABAergic currents in CA1 hippocampal pyramidal neurons. GABA-evoked chloride currents were measured in the presence or absence of L-NAME using whole-cell patch-clamp recordings in acute hippocampal slices from young adult mice. Enhancement of the tonic GABA responses induced by L-NAME was insensitive to TTX and decreased by co-incubation with the NO donor DEA/NO. Applications of DEA/NO alone did not produce significant effects on tonic GABA responses. L-NAME treatment also increased the amplitude of phasic GABAergic currents evoked by GABA-puffs. Our results indicate that the extent of tonic and phasic inhibition mediated by GABA(A) receptors in CA1 hippocampal pyramidal neurons is affected by endogenous NO production. (C) 2015 Elsevier Ireland Ltd. All rights reserved.