Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, PR China.
Eur J Pharmacol. 2010 Apr 10;631(1-3):10-6. doi: 10.1016/j.ejphar.2009.12.038. Epub 2010 Jan 11.
Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels have been suggested to play an important role in the control of membrane excitability and rhythmic neuronal activity. Our previous study showed that the selective HCN channels blocker, ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride) can block the induction of long-term potentiation (LTP) in perforant path-CA3 region in rat hippocampus in vivo. In the present study, we investigated the effect of ZD7288 on synaptic transmission and high frequency stimulation (HFS)-induced LTP in the Schaffer collateral-CA1 synapse of rat hippocampus in vivo, and examined the possible relations between activation of N-methyl-d-aspartate (NMDA) type of glutamate receptor and HCN channels for induction of LTP. Application of ZD7288 modulated synaptic transmission and produced a dose-dependent inhibition of the induction of LTP, and the inhibitory action was partially reversed by the application of NMDA. In addition, ZD7288, when given 30 min after HFS, did not alter the maintenance of LTP. The results suggest that ZD7288 has the ability to prevent the induction of LTP at the Schaffer collateral-CA1 synapse of rat hippocampus, and that this inhibitory effect is attenuated by direct activation of the NMDA receptor.
超极化激活环核苷酸门控 (HCN) 通道被认为在膜兴奋性和节律性神经元活动的控制中发挥重要作用。我们之前的研究表明，选择性 HCN 通道阻断剂 ZD7288（4-（N-乙基-N-苯基氨基）-1,2-二甲基-6-（甲氨基）嘧啶氯化物）可阻断体内大鼠海马穹窿- CA3 区长时程增强（LTP）的诱导。在本研究中，我们研究了 ZD7288 对体内大鼠海马 CA1 区 Schaffer 侧枝-CA1 突触传递和高频刺激（HFS）诱导的 LTP 的影响，并检查了 NMDA 型谷氨酸受体激活与 HCN 通道之间可能存在的关系对于 LTP 的诱导。ZD7288 的应用调节了突触传递，并产生了剂量依赖性的 LTP 诱导抑制作用，该抑制作用可部分被 NMDA 的应用逆转。此外，在 HFS 后 30 分钟给予 ZD7288 不会改变 LTP 的维持。结果表明，ZD7288 具有防止大鼠海马 Schaffer 侧枝-CA1 突触 LTP 诱导的能力，并且这种抑制作用可通过 NMDA 受体的直接激活而减弱。
