Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons

	Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons
	Gao J 1,2; Wu LJ 1,2; Xu L 3; Xu TL*1,2; tlxu@ion.ac.cn
	2004
发表期刊	BRAIN RESEARCH
ISSN	0006-8993
卷号	1017 期号:1-2 页码:197-207
合作性质	其它
摘要	The characterization of acid-sensing ion channel (ASIC)-like currents has been reported in hippocampal neurons in primary culture. However, it is suggested that the profile of expression of ASICs changes in culture. In this study, we investigated the properties of proton-activated current and its modulation by extracellular Ca2+ and Zn2+ in neurons acutely dissociated from the rat hippocampal CA1 using conventional whole-cell patch-clamp recording. A rapidly decaying inward current and membrane depolarization was induced by exogenous application of acidic solution. The current was sensitive to the extracellular proton with a response threshold of pH 7.0-6.8 and the pH(50) Of 6.1, the reversal potential close to the Na+ equilibrium potential. It had a characteristic of acid-sensing ion channels (ASICs) as demonstrated by its sensitivity to amiloride (IC50 = 19.6 +/- 2.1 muM). Either low [Ca2+](0) or high [Zn2+](0) increased the amplitude of the current. All these characteristics are consistent with a current mediated through a mixture of homomeric ASIC1a and heteromeric ASIC1a + 2a channels and closely replicate many of the characteristics that have been previously reported for hippocampal neurons cultured for a week or more, indicating that culture artifacts do not necessarily flaw the properties of ASICs. Interestingly, we found that high [Zn2+] (>10(-4) M) slowed the decay time constant of the ASIC-like current significantly in both acutely dissociated and cultured hippocampal neurons. In addition, the facilitating effects of low [Ca2+](0) and high [Zn2+](0) on the ASIC-like current were not additive. Since tissue acidosis, extracellular Zn elevation and/or Ca2+ reduction occur concurrently under some physiological and/or pathological conditions, the present observations suggest that hippocampal ASICs may offer a novel pharmacological target for therapeutic invention.
关键词	Proton-induced Current Acid-sensing Ion Channel Hippocampal Ca1 Neuron Patch-clamp
资助者	This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu. ; This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu. ; This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu. ; This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu.
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收录类别	SCI
语种	英语
资助者	This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu. ; This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu. ; This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu. ; This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2- SW-217) to T.-L. Xu.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/5855
专题	科研部门_学习记忆的分子神经机制（徐林）
通讯作者	tlxu@ion.ac.cn
作者单位	1.School of Life Sciences, University of Science and Technology of China, Hefei 230027, China 2.Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3.Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
推荐引用方式 GB/T 7714	Gao J,Wu LJ,Xu L,et al. Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons[J]. BRAIN RESEARCH,2004,1017(1-2):197-207.
APA	Gao J,Wu LJ,Xu L,Xu TL*,&tlxu@ion.ac.cn.(2004).Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons.BRAIN RESEARCH,1017(1-2),197-207.
MLA	Gao J,et al."Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons".BRAIN RESEARCH 1017.1-2(2004):197-207.

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