Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
Korean J Physiol Pharmacol. 2009 Dec;13(6):461-7. doi: 10.4196/kjpp.2009.13.6.461. Epub 2009 Dec 31.
The auditory cortex (A1) encodes the acquired significance of sound for the perception and interpretation of sound. Nitric oxide (NO) is a gas molecule with free radical properties that functions as a transmitter molecule and can alter neural activity without direct synaptic connections. We used whole-cell recordings under voltage clamp to investigate the effect of NO on spontaneous GABAergic synaptic transmission in mechanically isolated rat auditory cortical neurons preserving functional presynaptic nerve terminals. GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) in the A1 were completely blocked by bicuculline. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), reduced the GABAergic sIPSC frequency without affecting the mean current amplitude. The SNAP-induced inhibition of sIPSC frequency was mimicked by 8-bromoguanosine cyclic 3',5'-monophosphate, a membrane permeable cyclic-GMP analogue, and blocked by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a specific NO scavenger. Blockade of presynaptic K(+) channels by 4-aminopyridine, a K(+) channel blocker, increased the frequencies of GABAergic sIPSCs, but did not affect the inhibitory effects of SNAP. However, blocking of presynaptic Ca(2+) channels by Cd(2+), a general voltage-dependent Ca(2+) channel blocker, decreased the frequencies of GABAergic sIPSCs, and blocked SNAP-induced reduction of sIPSC frequency. These findings suggest that NO inhibits spontaneous GABA release by activation of cGMP-dependent signaling and inhibition of presynaptic Ca(2+) channels in the presynaptic nerve terminals of A1 neurons.
听觉皮层（A1）对声音进行编码，以感知和解释声音。一氧化氮（NO）是一种具有自由基性质的气体分子，作为一种递质分子起作用，可以在没有直接突触连接的情况下改变神经活动。我们使用全细胞膜片钳记录在电压钳下，研究 NO 对保留功能突触前神经末梢的机械分离的大鼠听觉皮层神经元中自发性 GABA 能突触传递的影响。A1 中的 GABA 能自发性抑制性突触后电流（sIPSCs）完全被荷包牡丹碱阻断。NO 供体 S-亚硝基-N-乙酰青霉胺（SNAP）降低 GABA 能 sIPSC 频率，而不影响平均电流幅度。8-溴鸟苷环 3'，5'-单磷酸，一种膜通透性环鸟苷酸类似物，模拟了 SNAP 诱导的 sIPSC 频率抑制，并被特异性 NO 清除剂 2-（4-羧基苯基）-4,4,5,5-四甲基咪唑啉-1-氧-3-氧化物阻断。4-氨基吡啶，一种 K(+) 通道阻断剂，阻断突触前 K(+) 通道，增加 GABA 能 sIPSCs 的频率，但不影响 SNAP 的抑制作用。然而，Cd(2+)，一种通用电压依赖性 Ca(2+) 通道阻断剂，阻断突触前 Ca(2+) 通道，降低 GABA 能 sIPSCs 的频率，并阻断 SNAP 诱导的 sIPSC 频率降低。这些发现表明，NO 通过激活 cGMP 依赖性信号和抑制突触前神经末梢的 Ca(2+) 通道来抑制 A1 神经元中自发性 GABA 释放。
