Li C, Peoples R W, Li Z, Weight F F
Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8264-7. doi: 10.1073/pnas.90.17.8264.
Despite the increasing recognition that ATP is an important extracellular excitatory mediator in the nervous system, the regulation of ATP receptors is poorly understood. Because the extracellular Zn2+ concentration is regulated in a variety of biological tissues, we studied modulation of the ATP-gated cation channel by Zn2+ in mammalian neurons using the whole-cell patch-clamp technique. In approximately 73% of cells tested, the amplitude of ATP-activated membrane ion current increased up to 5-fold in the presence of micromolar concentrations of Zn2+. The characteristics of this action suggest that Zn2+ increases the apparent affinity of the receptor for ATP. In addition, Zn2+ increased membrane depolarization and action potential firing elicited by ATP. These observations suggest that Zn2+ may play a physiological role in regulating the excitatory action of ATP on mammalian neurons.
尽管人们越来越认识到三磷酸腺苷(ATP)是神经系统中一种重要的细胞外兴奋性介质,但对ATP受体的调节却知之甚少。由于多种生物组织中细胞外锌离子(Zn2+)浓度受到调节,我们使用全细胞膜片钳技术研究了Zn2+对哺乳动物神经元中ATP门控阳离子通道的调节作用。在大约73%的测试细胞中,在微摩尔浓度的Zn2+存在下,ATP激活的膜离子电流幅度增加了高达5倍。这种作用的特性表明,Zn2+增加了受体对ATP的表观亲和力。此外,Zn2+增强了由ATP引起的膜去极化和动作电位发放。这些观察结果表明,Zn2+可能在调节ATP对哺乳动物神经元的兴奋性作用中发挥生理作用。