上海交通大学学报(医学版) ›› 2021, Vol. 41 ›› Issue (2): 154-158.doi: 10.3969/j.issn.1674-8115.2021.02.005

• 论著·基础研究 • 上一篇    下一篇

ATP敏感钾通道负向调节海马长时程增强的维持

张晓琳(), 张小云, 贺桂琴, 孔月, 周子凯()   

  1. 上海交通大学医学院附属精神卫生中心,上海 200030
  • 收稿日期:2020-03-30 出版日期:2021-02-28 发布日期:2021-02-28
  • 通讯作者: 周子凯 E-mail:1056372478@qq.com;zikai.zhou@live.com
  • 作者简介:张晓琳(1996—),女,硕士生;电子信箱:1056372478@qq.com
  • 基金资助:
    上海市教育委员会高峰高原学科建设计划(20191835);上海市优秀学科带头人计划(19XD1423300)

ATP-sensitive potassium channel negatively regulates hippocampal long-term potentiation maintenance

Xiao-lin ZHANG(), Xiao-yun ZHANG, Gui-qin HE, Yue KONG, Zi-kai ZHOU()   

  1. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
  • Received:2020-03-30 Online:2021-02-28 Published:2021-02-28
  • Contact: Zi-kai ZHOU E-mail:1056372478@qq.com;zikai.zhou@live.com
  • Supported by:
    Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20191835);Program of Shanghai Academic Research Leader(19XD1423300)

摘要:

目的·探讨ATP敏感钾通道(ATP-sensitive potassium channel,KATP)在突触可塑性实验模型长时程增强(long-term potentiation,LTP)的诱导和维持阶段的不同作用。方法·采用5~6周龄雄性C57BL/6小鼠,制备急性脑海马切片。在海马谢弗侧枝CA3-CA1投射通路以场电位的电生理记录方式检测KATP的开放激活对基础水平突触传递的影响;通过高频刺激诱导LTP并分别检测在诱导和维持阶段开放KATP对突触传递强度的影响;采用氧糖剥夺模型抑制脑片代谢水平以病理性激活KATP,并检测KATP阻断剂甲苯磺丁脲(tolbutamide,TOL)预处理对氧糖剥夺模型造成的海马LTP损伤的预防作用。结果·KATP的开放状态不影响基础水平的突触传递,也不影响LTP的诱导过程,但显著降低LTP维持阶段的幅度。TOL预处理可显著改善糖氧剥夺造成的LTP损伤。结论·KATP在生理和病理条件下均对海马LTP的维持起负向调节作用。

关键词: ATP敏感钾通道, 长时程增强, 突触可塑性

Abstract:

Objective·To investigate the regulatory roles of ATP-sensitive potassium channel (KATP) in the induction and maintenance stages of long-term potentiation (LTP), which is an experimental model for studies of synaptic plasticity and memory.

Methods·Acute brain slices were prepared from male C57BL/6 mice at 5?6 weeks of age. Electrophysiological recording of the field excitatory postsynaptic potentials was performed at the hippocampal Schaffer collateral-commissural pathway. KATP opener cromakalim was used to activate KATP at basal level, induction and maintenance stages of LTP. Oxygen-glucose deprivation (OGD) was used to induce hypoxia and pathological opening of KATP at the maintenance stage of LTP. Tolbutamide (TOL) was used to block KATP before OGD treatment.

Results·KATP opening showed no effects on basal synaptic transmission and the induction of LTP, but largely decreased the magnitude of LTP at maintenance stage. OGD rapidly impaired LTP maintenance, which was significantly prevented by TOL pre-treatment.

Conclusion·KATP negatively regulates hippocampal LTP maintenance in both physiological and pathological conditions.

Key words: ATP-sensitive potassium channel (KATP), long-term potentiation (LTP), synaptic plasticity

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