García-Colunga J, González-Herrera M, Miledi R
Centro de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla, Querétaro.
Neuroreport. 2001 Jan 22;12(1):147-50. doi: 10.1097/00001756-200101220-00037.
A study was made of the modulation of nicotinic acetylcholine receptors by the divalent cation zinc. Rat neuronal nicotinic receptors (alpha2beta4) were expressed in Xenopus oocytes and membrane currents evoked by acetylcholine (ACh currents) were recorded using a two microelectrode voltage clamp. In non-injected oocytes, or in oocytes expressing alpha2beta4 receptors, Zn2+ by itself (1 microM-4 mM) generated only very small membrane currents. In contrast, in oocytes expressing alpha2beta4 receptors, Zn2+ greatly and reversibly increased the ACh current, without affecting considerably its time course. The ACh current potentiation by Zn2+ was weakly dependent on the membrane potential (2.33+/-0.10 times the control current at -100 mV vs 2.04+/-0.06 at -60 mV, suggesting that Zn2+ interacts with the receptor in the vestibule of the ion channel or at an external domain of the protein. The inward rectification of control and Zn2+-potentiated ACh-currents was similar. We conclude that Zn2+ positively and reversibly modulates neuronal nicotinic receptors in a practically voltage-independent manner and without affecting their rate of desensitization. These results will help to understand better the roles played by Zn2+ in brain functions.
开展了一项关于二价阳离子锌对烟碱型乙酰胆碱受体调节作用的研究。大鼠神经元烟碱型受体（α2β4）在非洲爪蟾卵母细胞中表达，并使用双微电极电压钳记录乙酰胆碱诱发的膜电流（ACh电流）。在未注射的卵母细胞或表达α2β4受体的卵母细胞中，单独的Zn2 +（1μM - 4 mM）仅产生非常小的膜电流。相反，在表达α2β4受体的卵母细胞中，Zn2 +极大且可逆地增加了ACh电流，而对其时间进程没有显著影响。Zn2 +对ACh电流的增强作用对膜电位的依赖性较弱（在 - 100 mV时为对照电流的2.33±0.10倍，而在 - 60 mV时为2.04±0.06倍），这表明Zn2 +在离子通道前庭或蛋白质的外部结构域与受体相互作用。对照和Zn2 +增强的ACh电流的内向整流相似。我们得出结论，Zn2 +以几乎不依赖电压的方式正向且可逆地调节神经元烟碱型受体，且不影响其脱敏速率。这些结果将有助于更好地理解Zn2 +在脑功能中所起的作用。
