Nitric oxide inhibits spinally projecting paraventricular neurons through potentiation of presynaptic GABA release
Nitric oxide inhibits spinally projecting paraventricular neurons through potentiation of presynaptic GABA release
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DOI：
10.1152/jn.00540.2002
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发表时间：
2002-11-01
影响因子：
2.5
通讯作者：
Pan, HL
中科院分区：
文献类型：
--
作者：
Li, DP;Chen, SR;Pan, HL
室旁核（PVN）内的一氧化氮（NO）参与了PVN神经元兴奋性的调节。然而，NO对抑制性GABA能和兴奋性GABA能传入脊髓投射PVN神经元的影响还没有具体的研究。在本研究中，我们确定了抑制性GABA能和兴奋性GABA能输入在NO对脊髓投射PVN神经元的抑制作用中的作用。将荧光染料1，1 ′-双十八烷基-3，3，3 ′，3 ′-四甲基吲哚碳蓝（DiI）注射到大鼠脊髓内，逆行标记投射到脊髓的PVN神经元。在下丘脑切片中对DiI标记的PVN神经元进行全细胞电压和电流钳记录。20 μ M荷包牡丹碱可消除DiI标记神经元中记录的自发性微小抑制性突触后电流（mIPSC），而20 μ M 6-氰基-7-硝基喹喔啉-2，3-二酮可消除微小兴奋性突触后电流（mEPSC）。浴应用NO供体，100 μ M的S-亚硝基-N-乙酰基-青霉胺（SNAP），或NO前体，100 μ M的L-精氨酸，都显着增加的DiI标记的PVN神经元的mIPSC的频率，而不改变振幅和衰减时间常数的mIPSC。SNAP和L-精氨酸对mIPSCs频率的影响分别被NO清除剂2-（4-羧基苯基）-4，4，5，5-四甲基咪唑啉-1-氧基-3-氧化物和NO合成酶抑制剂1-（2-三氟甲基苯基）咪唑消除。SNAP和L-精氨酸均未显著改变mEPSCs的频率和振幅。在电流钳条件下，100 μ M SNAP或100 μ M L-精氨酸显著降低DiI标记的PVN神经元的放电速率，而不显著影响静息膜电位。另一方面，20 μ M荷包牡丹碱显著增加PVN神经元的冲动活动。在荷包牡丹碱存在下，SNAP或L-精氨酸都不能抑制PVN神经元的放电活动。这项电生理学研究提供了大量的新证据表明，NO通过增强GABA能突触输入抑制脊髓投射PVN神经元的活动。
Nitric oxide (NO) in the paraventricular nucleus (PVN) is involved in the regulation of the excitability of PVN neurons. However, the effect of NO on the inhibitory GABAergic and excitatory glutamatergic inputs to spinally projecting PVN neurons has not been studied specifically. In the present study, we determined the role of the inhibitory GABAergic and excitatory glutamatergic inputs in the inhibitory action of NO on spinally projecting PVN neurons. Spinally projecting PVN neurons were retrogradely labeled by a fluorescent dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocasbocyane (DiI), injected into the spinal cord of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled PVN neurons in the hypothalamic slice. The spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in DiI-labeled neurons were abolished by 20 muM bicuculline, whereas the miniature excitatory postsynaptic currents (mEPSCs) were eliminated by 20 muM 6-cyano-7-nitroquinoxaline-2,3-dione. Bath application of an NO donor, 100 muM S-nitroso-N-acetyl-penicillamine (SNAP), or the NO precursor, 100 muM L-arginine, both significantly increased the frequency of mIPSCs of DiI-labeled PVN neurons, without altering the amplitude and the decay time constant of mIPSCs. The effect of SNAP and L-arginine on the frequency of mIPSCs was eliminated by an NO scavenger, 2-(4-carboxypheny)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, and an NO synthase inhibitor, 1-(2-trifluoromethylphenyl) imidazole, respectively. Neither SNAP nor L-arginine significantly altered the frequency and the amplitude of mEPSCs. Under current-clamp conditions, 100 muM SNAP or 100 muM L-arginine significantly decreased the discharge rate of the DiI-labeled PVN neurons, without significantly affecting the resting membrane potential. On the other hand, 20 muM bicuculline significantly increased the impulse activity of PVN neurons. In the presence of bicuculline, SNAP or L-arginine both failed to inhibit the firing activity of PVN neurons. This electrophysiological study provides substantial new evidence that NO suppresses the activity of spinally projecting PVN neurons through potentiation of the GABAergic synaptic input.