Kimura S, Uchiyama S, Takahashi H E, Shibuki K
Department of Neurophysiology, Brain Research Institute, School of Medicine, Niigata University, Niigata 951-8585, Japan.
J Neurosci. 1998 Nov 1;18(21):8551-8. doi: 10.1523/JNEUROSCI.18-21-08551.1998.
Nitric Oxide (NO) is released from parallel fibers (PFs) after PF stimulation. NO-cGMP signaling is essential for long-term depression (LTD) in cerebellar PF-Purkinje cell synapses, which also exhibit presynaptic long-term potentiation (LTP) after tetanic PF stimulation. This LTP is dependent on cAMP but not NO-cGMP signaling. In this study, we analyzed long-term changes of NO release from PFs in rat cerebellar slices using electrochemical NO probes. Repetitive PF stimulation at 10 Hz for 2 sec elicited a transient increase in NO concentration (2.2 +/- 0.1 nM; mean +/- SEM; n = 116). This NO release exhibited long-term potentiation (LTPNO) by 36 +/- 3% (n = 15) after tetanic PF stimulation. Induction of LTPNO was not affected by Glu receptor antagonists. NO release from PFs was also potentiated by L-Arg (ARG) (100 microM), forskolin (50 microM), and 8-bromo-cAMP (Br-cAMP) (1 mM) but not by 1,9-dideoxyforskolin (50 microM), a biologically inactive analog of forskolin. The potentiation induced by forskolin was significantly suppressed by H89 (10 microM), a blocker of cAMP-dependent protein kinase. The potentiation induced by forskolin, but not that induced by Arg, interfered with LTPNO. H89 (10 microM) and KT5720 (1 microM), another blocker of cAMP-dependent protein kinase, but not KT5823 (300 nM), a blocker of cGMP-dependent protein kinase, significantly suppressed LTPNO. These data indicate that neural NO release is under activity-dependent control, just as synaptic transmitter release is. LTPNO might play a role in cross talk between presynaptic and postsynaptic plasticity by facilitating NO-cGMP-dependent postsynaptic LTD after induction of cAMP-dependent presynaptic LTP and LTPNO.
在平行纤维（PFs）受到刺激后，一氧化氮（NO）会从PFs中释放出来。NO - cGMP信号传导对于小脑PF - 浦肯野细胞突触中的长时程抑制（LTD）至关重要，在强直刺激PFs后，该突触也会表现出突触前长时程增强（LTP）。这种LTP依赖于cAMP而非NO - cGMP信号传导。在本研究中，我们使用电化学NO探针分析了大鼠小脑切片中PFs释放NO的长期变化。以10Hz的频率对PFs进行2秒的重复刺激会引起NO浓度的短暂升高（2.2±0.1 nM；平均值±标准误；n = 116）。在强直刺激PFs后，这种NO释放表现出长期增强（LTPNO），增强幅度为36±3%（n = 15）。LTPNO的诱导不受谷氨酸受体拮抗剂的影响。PFs释放的NO也会被L - 精氨酸（ARG）（100μM）、福斯高林（50μM）和8 - 溴 - cAMP（Br - cAMP）（1 mM）增强，但不会被1,9 - 二脱氧福斯高林（50μM）增强，1,9 - 二脱氧福斯高林是福斯高林的一种无生物学活性的类似物。福斯高林诱导的增强作用被H89（10μM）显著抑制，H89是一种环磷酸腺苷（cAMP）依赖性蛋白激酶的阻滞剂。福斯高林诱导的增强作用，而非精氨酸诱导的增强作用，会干扰LTPNO。H89（10μM）和另一种cAMP依赖性蛋白激酶的阻滞剂KT5720（1μM），但不是环磷酸鸟苷（cGMP）依赖性蛋白激酶的阻滞剂KT5823（300 nM），显著抑制LTPNO。这些数据表明，神经NO释放如同突触递质释放一样，受到活动依赖性控制。LTPNO可能通过在诱导cAMP依赖性突触前LTP和LTPNO后促进NO - cGMP依赖性突触后LTD，在突触前和突触后可塑性之间的相互作用中发挥作用。
