中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (5): 779-786.doi: 10.4103/1673-5374.182705

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

影响海马突触传递的超极化激活环核苷酸门控阳离子通道阻滞剂ZD7288

  

  • 收稿日期:2015-12-22 出版日期:2016-05-20 发布日期:2016-05-20
  • 基金资助:

    国家自然科学基金项目(81173038, 81001425)

ZD7288, a selective hyperpolarizationactivated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity

Xiao-xue Zhang1, #, Xiao-chun Min1, #, Xu-lin Xu2, Min Zheng3, *, Lian-jun Guo2, *   

  1. "1 Department of Laboratory Medicine, Affiliated Pu’ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China 2 Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China 3 School of Biomedical Engineering, Hubei University of Science and Technology, Xianning, Hubei Province, China"
  • Received:2015-12-22 Online:2016-05-20 Published:2016-05-20
  • Contact: Min Zheng or Lian-jun Guo, ljguo@hust.edu.cn.
  • Supported by:

    This work was supported by grants from the National Natural Science Foundation of China, No. 81173038, 81001425.

摘要:

ZD7288作为一种选择性超极化激活环核苷酸门控阳离子通道阻断剂,能阻断大鼠体内穿通纤维通路-海马CA3区长时程增强的诱导,为进一步了解其作用机制。我们首先记录了雄性SD大鼠的穿通纤维通路-海马CA3区场的兴奋性突触后电位,然后使用高效液相色谱分析海马组织和培养海马神经元中谷氨酸的含量,并利用Fura-2检测细胞内钙离子浓度。发现ZD7288能抑制长时程增强的诱导和维持,且与已知的超极化激活环核苷酸门控阳离子通道非特异性阻断剂CsCl的作用类似。此外,ZD7288减少海马组织和培养的海马神经元中谷氨酸的释放,呈浓度依赖性减少谷氨酸所致钙内流,扭转了cAMP 类似物8-Br-cAMP介导的钙内流变化。说明ZD7288通道通过对海马神经元谷氨酸的释放以及谷氨酸所致钙内流,而影响海马突触传递功能。

orcid: 0000-0001-9708-6442(Lian-jun Guo)

关键词: 神经再生, ZD7288, Ih通道, 穿通纤维通路-海马CA3区突触, 长时程增强, 场兴奋性突触后电位, 谷氨酸释放

Abstract:

"The selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimethyl- 6-(methylamino) pyrimidinium chloride (ZD7288) blocks the induction of long-term potentiation in the perforant path–CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path–CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca2+ concentration ([Ca2+]i) using Fura- 2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspecific HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Furthermore, ZD7288 attenuated glutamate-induced rises in [Ca2+]i in a concentration-dependent manner and reversed 8-Br-cAMP-mediated facilitation of these glutamate-induced [Ca2+]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both glutamate release and resultant [Ca2+]i increases in rat hippocampal neurons."

Key words: "nerve regeneration, ZD7288, Ih channels, perforant path–CA3 synapse, long-term potentiation, field excitatory postsynaptic potentials, glutamate release, neural regeneration"