Zinc-mediated attenuation of hippocampal mossy fiber long-term potentiation induced by forskolin
Zinc-mediated attenuation of hippocampal mossy fiber long-term potentiation induced by forskolin
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DOI：
10.1016/j.neuint.2010.07.010
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发表时间：
2010-11-01
影响因子：
4.2
通讯作者：
Takeda, Atsushi
中科院分区：
文献类型：
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作者：
Ando, Masaki;Oku, Naoto;Takeda, Atsushi
高频刺激引起的突触前钙升高激活钙-钙调素敏感腺苷酸环化酶（AC） 1，随后诱导海马苔藓纤维- cm突触的长期增强（LTP）。锌与谷氨酸一起从苔藓状纤维末端释放。然而，锌在苔藓纤维LTP中的作用存在争议。本研究在交流活化剂福斯克林诱导下，探讨了锌介导的苔藓纤维LIP衰减机制。5 μ M ZnCl2存在时，100 Hz 1 s的强电刺激诱导的苔藓纤维LTP有衰减，而0.1 Hz的试验刺激下，弗斯可林诱导的苔藓纤维LTP无衰减。诱导前灌注100 μ M ZnCl2可减弱福斯克林诱导的苔藓纤维LIP。然而，锌（100 μ M）预灌注没有减弱蛋白激酶A激活剂sp - camp诱导的苔藓纤维LIP。锌是苔藓纤维钮扣中必需的，以有效地抑制AC活性。在用ZnAF-2 DA（一种膜透性锌指示剂）标记的海马切片中，在5 μ M ZnCl2存在的强直刺激下，细胞内ZnAF-2信号增加，但在测试刺激下没有增加。在100 μ M ZnCl2的刺激下，细胞内ZnAF-2信号增强。这些结果表明，锌被吸收到苔藓纤维中通过抑制AC活性来减弱福斯克林诱导的苔藓纤维LIP。重点讨论了破伤风诱导的苔藓纤维LIP对内源锌吸收的意义。(C) 2010 Elsevier Ltd.版权所有。
The rise in presynaptic calcium induced by high-frequency stimulation activates the calcium-calmodulin-sensitive adenylyl cyclase (AC) 1 followed by the induction of long-term potentiation (LTP) at the hippocampal mossy fiber-CM synapse. Zinc is released with glutamate from mossy fiber terminals. However, the role of the zinc in mossy fiber LTP is controversial. In the present study, the mechanism of zinc-mediated attenuation of mossy fiber LIP was examined in that induced by forskolin, an AC activator. Mossy fiber LTP induced by tetanic stimulation (100 Hz for 1 s) was attenuated in the presence of 5 mu M ZnCl2, whereas that induced by forskolin under test stimulation (0.1 Hz) was not attenuated. Forskolin-induced mossy fiber LIP was attenuated by perfusion with 100 mu M ZnCl2 prior to the induction. However, the zinc (100 mu M) pre-perfusion did not attenuate mossy fiber LIP induced by Sp-cAMPS, an activator of protein kinase A, under test stimulation. Zinc is necessary to be taken up into mossy fiber boutons for effectively inhibiting AC activity. In hippocampal slices labeled with ZnAF-2 DA, a membrane-permeable zinc indicator, intracellular ZnAF-2 signal was increased during tetanic stimulation in the presence of 5 mu M ZnCl2, but not under test stimulation. Intracellular ZnAF-2 signal was increased under test stimulation in the presence of 100 mu M ZnCl2. These results suggest that zinc taken up into mossy fibers attenuates forskolin-induced mossy fiber LIP via inhibition of AC activity. The significance of endogenous zinc uptake by mossy fibers is discussed focused on tetanus-induced mossy fiber LIP. (C) 2010 Elsevier Ltd. All rights reserved.