cAMP-Dependent Long-Term Potentiation of Nitric Oxide Release from Cerebellar Parallel Fibers in Rats
cAMP-Dependent Long-Term Potentiation of Nitric Oxide Release from Cerebellar Parallel Fibers in Rats
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DOI：
10.1523/jneurosci.18-21-08551.1998
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发表时间：
1998-11
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影响因子：
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通讯作者：
S. Kimura;S. Uchiyama;H. Takahashi;K. Shibuki
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作者：
S. Kimura;S. Uchiyama;H. Takahashi;K. Shibuki
刺激PF后，平行纤维(PF)释放一氧化氮(NO)。NO-cGMP信号在小脑PF-Purkinje细胞突触的长时抑制(LTD)中起重要作用，强直性Pf刺激后突触前长时程增强(LTP)也表现出来。这种LTP依赖于cAMP信号，而不依赖于NO-cGMP信号。在这项研究中，我们用电化学NO探针分析了大鼠小脑片PFS释放NO的长期变化。重复频率为10 Hz的PF刺激2s可引起一过性的NO浓度升高(2.2±0.1 nm；平均值±扫描电子显微镜；n=116)。强直性PF刺激后，这种释放的NO表现出36±3%的长时程增强(LTPNO)。Glu受体拮抗剂不影响LTPNO的诱导。L-精氨酸(Arg)(100μm)、Forsklin(50μm)和8-溴-cAMP(BR-cAMP)(1 MM)也可促进PFS的NO释放，但1，9-二脱氧Forsklin(50μm)对其无明显影响。CAMP依赖的蛋白激酶阻断剂H89(10μm)可显著抑制Forskolin的增强作用。Forskolin诱导的增强作用对LTPNO有干扰作用，而Arg则无此作用。另一种cAMP依赖性蛋白激酶阻断剂KT5720(1μm)和H89(10μm)对LTPNO有明显抑制作用，而cGMP依赖性蛋白激酶阻断剂KT5823(300 Nm)对LTPNO无明显抑制作用。这些数据表明，神经NO释放受到活动依赖的控制，就像突触递质的释放一样。LTPNO可能通过促进cAMP依赖的突触前LTP和LTPNO诱导的突触后LTD在突触前和突触后可塑性之间的串扰发挥作用。
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 μm), forskolin (50 μm), and 8-bromo-cAMP (Br-cAMP) (1 mm) but not by 1,9-dideoxyforskolin (50 μm), a biologically inactive analog of forskolin. The potentiation induced by forskolin was significantly suppressed by H89 (10 μm), a blocker of cAMP-dependent protein kinase. The potentiation induced by forskolin, but not that induced by Arg, interfered with LTPNO. H89 (10 μm) and KT5720 (1 μm), 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.