Department of Biological Science and Program, Florida State University, Tallahassee, FL 32306, USA.
Neuroscience. 2011 Jul 14;186:32-8. doi: 10.1016/j.neuroscience.2011.04.021. Epub 2011 Apr 22.
Glycine receptors are widely expressed in the mammalian central nervous system, and previous studies have demonstrated that glycine receptors are modulated by endogenous zinc. Zinc is concentrated in synaptic vesicles in several brain regions but is particularly abundant in the hippocampus and olfactory bulb. In the present study, we used patch-clamp electrophysiology of rat hippocampal and olfactory bulb neurons in primary culture to examine the effects of zinc on glycine receptors. Although glycine has been reported to reach millimolar concentrations during synaptic transmission, most previous studies on the effects of zinc on glycine receptors have used relatively low concentrations of glycine. High concentrations of glycine cause receptor desensitization. Our current results extend our previous demonstration that the modulatory actions of zinc are largely prevented when co-applied with desensitizing concentrations of glycine (300 μM), suggesting that the effects of zinc are dependent on the state of the receptor. In contrast, pre-application of 300 μM zinc, prior to glycine (300 μM) application, causes a slowly developing inhibition with a slow rate of recovery, suggesting that the timing of zinc and glycine release also influences the effects of zinc. Furthermore, previous evidence suggests that synaptically released zinc can gain intracellular access, and we provide the first demonstration that low concentrations of intracellular zinc can potentiate glycine receptors. These results support the notion that zinc has complex effects on glycine receptors and multiple factors may interact to influence the efficacy of glycinergic transmission.
甘氨酸受体广泛表达于哺乳动物中枢神经系统，先前的研究表明甘氨酸受体受内源性锌的调节。锌在几个脑区的突触小泡中浓缩，但在海马体和嗅球中特别丰富。在本研究中，我们使用原代培养的大鼠海马体和嗅球神经元的膜片钳电生理学技术，研究锌对甘氨酸受体的影响。尽管已有报道称在突触传递过程中甘氨酸可达到毫摩尔浓度，但以前关于锌对甘氨酸受体影响的大多数研究都使用相对较低浓度的甘氨酸。高浓度的甘氨酸会导致受体脱敏。我们目前的结果扩展了我们之前的研究结果，即在应用脱敏浓度（300μM）的甘氨酸时，锌的调节作用在很大程度上被阻止，这表明锌的作用取决于受体的状态。相比之下，在应用 300μM 的甘氨酸之前预先应用 300μM 的锌会导致缓慢发展的抑制作用，恢复缓慢，这表明锌和甘氨酸释放的时间也会影响锌的作用。此外，先前的证据表明突触释放的锌可以获得细胞内的进入途径，我们首次证明了细胞内低浓度的锌可以增强甘氨酸受体。这些结果支持锌对甘氨酸受体具有复杂影响的观点，并且多种因素可能相互作用以影响甘氨酰能传递的功效。
