我系的研究论文《Activity-dependent downregulation of M-Type (Kv7) K⁺channels surface expression requires the activation of iGluRs/Ca2⁺/PKC signaling pathway in hippocampal neuron》于2015年8月在药理学权威杂志《Neuropharmacology》发表。该研究工作由博士生李彩和副教授吕青等在徐旭林副教授和郭莲军教授的指导下完成。

Kv7通道在调节神经元兴奋和突触可塑性等作用中起重要作用，但是神经元活动是否调控Kv7通道的转运及其分子机制目前还不清楚。该研究工作表明神经元兴奋可导致海马神经元细胞膜表面Kv7通道下调，Kv7通道活动依赖性表达下调可能与激活谷氨酸受体（NMDA和AMPA受体）-Ca²⁺-蛋白激酶C信号通路有关；细胞膜表面Kv7通道的活动依赖性表达下调参与调控海马神经元的突触可塑性和学习记忆活动。该研究工作证实离子型谷氨酸受体-Ca²⁺-蛋白激酶C信号通路介导的海马神经元功能性Kv7通道活动依赖性的表达下调是调节海马神经元兴奋性与突触可塑性的分子机制之一，为神经元兴奋性的调控和相关疾病的预防和治疗提供新的思路和策略。

论文链接：http://www.sciencedirect.com/science/article/pii/S0028390815000969

附：

Neuropharmacology. 2015 Aug;95:154-67. doi: 10.1016/j.neuropharm.2015.03.004. Epub 2015 Mar 18.

Activity-dependent downregulation of M-Type (Kv7) K⁺channels surface expression requires the activation of iGluRs/Ca²⁺/PKC signaling pathway in hippocampal neuron.

Li C¹, Lu Q², Huang P¹, Fu T¹, Li C¹, Guo L², Xu X³.

Abstract

M-type (Kv7) K(+) channels, encoded by KCNQ2-KCNQ5 genes, play a pivotal role in controlling neuronal excitability. However, precisely how neuronal activity regulates Kv7 channel translocation has not yet been fully defined. Here we reported activity-dependent changes in Kv7 channel subunits Kv7.2 and Kv7.3 surface expression by glutamate (glu). In the present study, we found that treatment with glutamate rapidly caused a specific decrease in M-current as well as Kv7 channel surface expression in primary cultured hippocampal neurons. The glutamate effects were mimicked by NMDA and AMPA. The glutamate effects on Kv7 channels were partially attenuated by pre-treatment of NMDA receptors antagonist d,l-APV or AMPA-KA receptors antagonist CNQX. The signal required Ca(2+) influx through L-type Ca(2+) channel and intracellular Ca(2+) elevations. PKC activation was involved in the glutamate-induced reduction of Kv7 channel surface expression. Moreover, a significant reduction of Kv7 channel surface expression occurred following glycine-induced "chem"-LTP in vitro and hippocampus-dependent behavioral learning training in vivo. These results demonstrated that activity-dependent reduction of Kv7 channel surface expression through activation of ionotropic glutamate receptors (iGluRs)/Ca(2+)/PKC signaling pathway might be an important molecular mechanism for regulation of neuronal excitability and synaptic plasticity.

KEYWORDS:

Excitability; Glutamate; Kv7 channels; NMDA and AMPA receptors; PKC; Surface expression