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
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DOI：
10.1016/j.brainres.2004.05.046
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发表时间：
2004-08-13
期刊：
影响因子：
2.9
通讯作者：
Xu, TL
中科院分区：
文献类型：
--
作者：
Gao, J;Wu, LJ;Xu, TL
原代培养的海马神经元中酸敏感离子通道（ASIC）样电流的特征已被报道。然而，有人认为 ASIC 的表达谱在文化中会发生变化。在本研究中，我们使用传统的全细胞膜片钳记录技术研究了与大鼠海马 CA1 急性分离的神经元中质子激活电流的特性及其细胞外 Ca2+ 和 Zn2+ 的调节。通过外源施加酸性溶液诱导快速衰减的内向电流和膜去极化。电流对细胞外质子敏感，响应阈值为pH 7.0-6.8，pH(50)为6.1，反转电位接近Na+平衡电位。它具有酸敏感离子通道 (ASIC) 的特性，如其对阿米洛利的敏感性 (IC50 = 19.6 +/- 2.1 muM) 所示。低 [Ca2+](0) 或高 [Zn2+](0) 都会增加电流的幅度。所有这些特征都与通过同聚 ASIC1a 和异聚 ASIC1a + 2a 通道混合介导的电流一致，并且紧密复制了先前报道的培养一周或更长时间的海马神经元的许多特征，表明培养伪影不一定会缺陷 ASIC 的特性。有趣的是，我们发现高[Zn2+] (>10(-4) M) 显着减缓了急性分离和培养的海马神经元中类ASIC 电流的衰减时间常数。此外，低[Ca2+](0)和高[Zn2+](0)对类ASIC电流的促进作用不是相加的。由于组织酸中毒、细胞外Zn升高和/或Ca2+减少在一些生理和/或病理条件下同时发生，目前的观察结果表明海马ASIC可以为治疗发明提供新的药理学靶点。 (C) 2004 Elsevier B.V. 保留所有权利。
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. (C) 2004 Elsevier B.V. All rights reserved.