Zinc modulation of glycine receptors.
Zinc modulation of glycine receptors.
复制标题
DOI：
10.1016/j.neuroscience.2011.04.021
复制
发表时间：
2011-07-14
期刊：
影响因子：
3.3
通讯作者：
Hill, B. J.
中科院分区：
文献类型：
--
作者：
Trombley, P. Q.;Blakemore, L. J.;Hill, B. J.
甘氨酸受体在哺乳动物中枢神经系统中广泛表达，先前的研究表明甘氨酸受体受内源性锌的调节。锌集中在几个大脑区域的突触囊泡中，但在海马和嗅球中特别丰富。在本研究中，我们采用膜片钳电生理在原代培养的大鼠海马和嗅球神经元的甘氨酸受体的影响，研究锌。虽然甘氨酸已被报道在突触传递过程中达到毫摩尔浓度，大多数以前的研究锌对甘氨酸受体的影响使用相对较低浓度的甘氨酸。高浓度的甘氨酸导致受体脱敏。我们目前的结果扩展了我们先前的证明，即当与脱敏浓度的甘氨酸（300 μM）共同应用时，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，在甘氨酸（300 μM）给药前预先给药300 μM锌会导致缓慢发展的抑制作用，恢复速度缓慢，表明锌和甘氨酸释放的时间也会影响锌的作用。此外，以前的证据表明，突触释放的锌可以获得细胞内的访问，我们提供了第一个证明，低浓度的细胞内锌可以增强甘氨酸受体。这些结果支持了锌对甘氨酸受体具有复杂作用的观点，并且多种因素可能相互作用以影响甘氨酸能传递的功效。
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.
登录
查看更多内容
影响因子：
2.5
作者：
Horning, MS;Trombley, PQ
通讯作者：
Trombley, PQ
影响因子：
4.8
作者：
Nevin, ST;Cromer, BA;Lynch, JW
通讯作者：
Lynch, JW
影响因子：
4.4
作者：
Balaji, RV;Colvin, RA
通讯作者：
Colvin, RA
影响因子：
3.3
作者：
Rigo, J. -M.;Legendre, P.
通讯作者：
Legendre, P.
影响因子：
64.8
作者：
ASSAF, SY;CHUNG, SH
通讯作者：
CHUNG, SH