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Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study

文献类型：期刊论文

作者Zhou, Shang-lin1,3; Chu, Hong-yuan1,3; Jin, Guo-zhang1; Cui, Jian-min2,4; Zhen, Xue-chu1,2,4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2014-06
卷号35期号:6页码:738-751
ISSN号1671-4083
关键词SKF83959 hippocampus pyramidal neuron neuronal modeling excitability Na+ channel EPSP temporal summation
DOI10.1038/aps.2014.23
文献子类Article
英文摘要Aim: 3-Methyl-6-chloro-7,8-hydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) have been shown to affect several types of voltage-dependent channels in hippocampal pyramidal neurons. The aim of this study was to determine how. modulation of a individual type of the channels by SKF83959 contributes to the overall excitability of CA1 pyramidal neurons during either direct current injections or synaptic activation. Methods: Rat hippocampal slices were prepared. The kinetics of voltage-dependent Na+ channels and neuronal excitability and depolarization block in CA1 pyramidal neurons were examined using whole-cell recording. A realistic mathematical model of hippocampal CA1 pyramidal neuron was used to simulate the effects of SKF83959 on neuronal excitability. Results: SKF83959 (50 mu mol/L) shifted the inactivation curve of Na+ current by 10.3 mV but had no effect on the activation curve in CA1 pyramidal neurons. The effects of SKF83959 on passive membrane properties, including a decreased input resistance and depolarized resting potential, predicted by our simulations were in agreement with the experimental data. The simulations showed that decreased excitability of the soma by SKF83959 (examined with current injection at the soma) was only observed when the membrane potential was compensated to the control levels, whereas the decreased dendritic excitability (examined with current injection at the dendrite) was found even without membrane potential compensation, which led to a decreased number of action potentials initiated at the soma. Moreover, SKF83959 significantly facilitated depolarization block in CA1 pyramidal neurons. SKF83959 decreased EPSP temporal summation and, of physiologically greater relevance, the synaptic-driven firing frequency. Conclusion: SKF83959 decreased the excitability of CA1.pyramidal neurons even though the drug caused the membrane potential depolarization. The results may reveal a partial mechanism for the drug's anti-Parkinsonian effects and may also suggest that SKF83959 has a potential antiepileptic effect.
WOS关键词EXCITATORY SYNAPTIC-TRANSMISSION ; DEPOLARIZATION BLOCK ; DOPAMINE-RECEPTOR ; RAT HIPPOCAMPUS ; POTASSIUM CHANNELS ; ACTION-POTENTIALS ; H-CHANNELS ; D-1 ; INHIBITION ; MECHANISMS
资助项目National Natural Science Foundation of China[81130023] ; National Natural Science Foundation of China[31373382] ; National Natural Science Foundation of China[31271143] ; National Basic Research Plan (973) of the Ministry of Science and Technology of China[2011CB5C4403] ; Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD)[00000000]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5156622
出版者ACTA PHARMACOLOGICA SINICA
WOS记录号WOS:000337267800004
源URL[http://119.78.100.183/handle/2S10ELR8/277048]  
专题药理学第二研究室
通讯作者Zhou, Shang-lin
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol 2, Shanghai 201203, Peoples R China;
2.Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Suzhou 215123, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
4.Soochow Univ, Coll Pharmaceut Sci, Jiangsu Key Lab Translat Res & Therapy Neuropsych, Suzhou 215123, Peoples R China;
推荐引用方式
GB/T 7714		 Zhou, Shang-lin,Chu, Hong-yuan,Jin, Guo-zhang,et al. Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study[J]. ACTA PHARMACOLOGICA SINICA,2014,35(6):738-751.
APA Zhou, Shang-lin,Chu, Hong-yuan,Jin, Guo-zhang,Cui, Jian-min,&Zhen, Xue-chu.(2014).Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study.ACTA PHARMACOLOGICA SINICA,35(6),738-751.
MLA Zhou, Shang-lin,et al."Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study".ACTA PHARMACOLOGICA SINICA 35.6(2014):738-751.

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来源：上海药物研究所

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