Hu W-P, Li X-M, Chen J-G, Li Z-W
Department of Physiology, Xianning College, Xianning 437100, PR China.
Neuroscience. 2007 Oct 12;149(1):1-6. doi: 10.1016/j.neuroscience.2007.07.018. Epub 2007 Jul 20.
Aluminum (Al(3+)), a known neurotoxic substance, has long been implicated in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases. Al(3+) targets many ligand-gated and voltage-gated ion channels and modulates their functions. In the present study, the actions of Al(3+) on the nicotinic acetylcholine receptor (nAChR) were investigated by whole-cell patch clamp technique in acutely isolated rat trigeminal ganglion neurons. We observed that Al(3+) potentiated nicotine-evoked inward currents in a concentration-dependent manner (10-1000 microM). The effects of Al(3+) on nicotine-evoked currents were voltage independent. Al(3+) appeared to increase the affinity of nicotine to nAChR but not the efficacy. Al(3+) reduced the agonist concentration producing a half-maximal response (EC(50)) for nicotine from 74.4+/-1.9 microM to 32.9+/-2.6 microM, but did not alter the threshold nor maximal response. On the contrary, another trivalent cation, Ga(3+), had little effect on nicotine-evoked currents. The present results indicated that Al(3+) enhanced the function of nAChR and this potentiation might underlie the neurological alteration induced by Al(3+).
铝离子（Al(3+)）是一种已知的神经毒性物质，长期以来一直被认为与阿尔茨海默病和其他神经退行性疾病的发病机制有关。Al(3+)作用于许多配体门控和电压门控离子通道并调节其功能。在本研究中，采用全细胞膜片钳技术在急性分离的大鼠三叉神经节神经元中研究了Al(3+)对烟碱型乙酰胆碱受体（nAChR）的作用。我们观察到Al(3+)以浓度依赖的方式（10 - 1000微摩尔）增强烟碱诱发的内向电流。Al(3+)对烟碱诱发电流的影响与电压无关。Al(3+)似乎增加了烟碱对nAChR的亲和力，但不影响其效能。Al(3+)使产生烟碱半数最大反应（EC(50)）的激动剂浓度从74.4±1.9微摩尔降低到32.9±2.6微摩尔，但未改变阈值和最大反应。相反，另一种三价阳离子Ga(3+)对烟碱诱发的电流几乎没有影响。目前的结果表明，Al(3+)增强了nAChR的功能，这种增强作用可能是Al(3+)诱导神经改变的基础。
