Neural Regeneration Research ›› 2016, Vol. 11 ›› Issue (5): 779-786.doi: 10.4103/1673-5374.182705

Previous Articles     Next Articles

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.

PDF

1252

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"