ATP敏感钾通道负向调节海马长时程增强的维持

doi:10.3969/j.issn.1674-8115.2021.02.005

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

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()

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()

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/Abstract

摘要：

目的·探讨ATP敏感钾通道（ATP-sensitive potassium channel，K_ATP）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K_ATP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K_ATP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K_ATP，并检测K_ATP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·K_ATP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·K_ATP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 (K_ATP) 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. K_ATP opener cromakalim was used to activate K_ATP at basal level, induction and maintenance stages of LTP. Oxygen-glucose deprivation (OGD) was used to induce hypoxia and pathological opening of K_ATP at the maintenance stage of LTP. Tolbutamide (TOL) was used to block K_ATP before OGD treatment.

Results·K_ATP 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·K_ATP negatively regulates hippocampal LTP maintenance in both physiological and pathological conditions.

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

中图分类号:

R338

张晓琳, 张小云, 贺桂琴, 孔月, 周子凯. ATP敏感钾通道负向调节海马长时程增强的维持[J]. 上海交通大学学报(医学版), 2021, 41(2): 154-158.

Xiao-lin ZHANG, Xiao-yun ZHANG, Gui-qin HE, Yue KONG, Zi-kai ZHOU. ATP-sensitive potassium channel negatively regulates hippocampal long-term potentiation maintenance[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(2): 154-158.

图/表 3

图1 KATP开放剂CRO不改变基础水平的突触传递Note:A. I-O curve. B. PPF curve.

Fig 1 KATP opener CRO did not modify synaptic properties at basal level.

图2 KATP开放剂CRO选择性降低LTP维持阶段的fEPSP幅度Note:A. Perfusion of KATP opener CRO (100 μmol/L) and KATP blocker TOL (50 μmol/L) during baseline recording and the first 10 min after high-frequency stimulation (HFS) did not affect LTP induction and maintenance. B. CRO perfusion at the LTP maintenance period significantly reduced fEPSP slope.

Fig 2 KATP opener CRO selectively reduced LTP magnitude at the maintenance stage

图3 OGD损伤LTP的维持过程且可通过阻断KATP预防Note:A. Five min perfusion of 95% N2/5% CO2 pre-saturated glucose-free artificial cerebrospinal fluid drastically impaired LTP magnitude at the maintenance stage. B. Ten min pre-treatment of KATP blocker TOL (50 μmol/L) significantly prevented OGD-induced LTP impairment.

Fig 3 OGD impaired LTP maintenance that can be largely prevented by pre-treatment of KATP blocker

参考文献 16

1	Bannerman DM, Sprengel R, Sanderson DJ, et al. Hippocampal synaptic plasticity, spatial memory and anxiety[J]. Nat Rev Neurosci, 2014, 15(3): 181.
2	Diering GH, Huganir RL. The AMPA receptor code of synaptic plasticity[J]. Neuron, 2018, 100(2): 314-329.
3	Kessels HW, Malinow R. Synaptic AMPA receptor plasticity and behavior[J]. Neuron, 2009, 61(3): 340-350.
4	Zhou Z, Liu A, Xia S, et al. The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning[J]. Nat Neurosci, 2018, 21(1): 50-62.
5	Nicoll RA. A brief history of long-term potentiation[J]. Neuron, 2017, 93(2): 281-290.
6	Lisman J, Yasuda R, Raghavachari S. Mechanisms of CaMKⅡaction in long-term potentiation[J]. Nat Rev Neurosci, 2012, 13(3): 169-182.
7	Pastalkova E, Serrano P, Pinkhasova D, et al. Storage of spatial information by the maintenance mechanism of LTP[J]. Science, 2006, 313(5790): 1141-1144.
8	Shema R, Sacktor TC, Dudai Y. Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKMζ[J]. Science, 2007, 317(5840): 951-953.
9	Tsokas P, Hsieh C, Yao Y, et al. Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice[J]. eLife, 2016, 5: e14846.
10	Wang S, Sheng T, Ren S, et al. Distinct roles of PKCι/λ and PKMζ in the initiation and maintenance of hippocampal long-term potentiation and memory[J]. Cell Rep, 2016, 16(7): 1954-1961.
11	Hibino H, Inanobe A, Furutani K, et al. Inwardly rectifying potassium channels: their structure, function, and physiological roles[J]. Physiol Rev, 2010, 90(1): 291-366.
12	Nichols CG. KATP channels as molecular sensors of cellular metabolism[J]. Nature, 2006, 440(7083): 470-476.
13	Yamada K, Ji JJ, Yuan H, et al. Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure[J]. Science, 2001, 292(5521): 1543-1546.
14	Schiemann J, Schlaudraff F, Klose V, et al. K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration[J]. Nat Neurosci, 2012, 15(9): 1272-1280.
15	Moriguchi S, Ishizuka T, Yabuki Y, et al. Blockade of the K_ATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer's disease therapy[J]. Mol Psychiatry, 2018, 23(2): 211-221.
16	Wu XF, Liu WT, Liu YP, et al. Reopening of ATP-sensitive potassium channels reduces neuropathic pain and regulates astroglial gap junctions in the rat spinal cord[J]. Pain, 2011, 152(11): 2605-2615.

[1]	刘大为1，任力2，闵苏2. Ⅰ型促代谢性谷氨酸受体在小剂量氯胺酮保护抑郁大鼠电休克后学习记忆功能中的作用[J]. 上海交通大学学报（医学版）, 2019, 39(11): 1248-.
[2]	黄悦琦，彭代辉. 钙/钙调蛋白依赖性蛋白激酶Ⅱ在抑郁症中的作用机制研究[J]. 上海交通大学学报（医学版）, 2015, 35(9): 1389-.
[3]	李强. NMDA受体与学习记忆关系的研究进展[J]. , 2010, 30(10): 1285-.

ATP敏感钾通道负向调节海马长时程增强的维持

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

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 16

相关文章 3

编辑推荐

Metrics