van Zundert Brigitte, Castro Patricio, Aguayo Luis G
Department of Physiology, University of Concepción, Laboratory of Neurophysiology, P.O. Box 160-C, Concepción, Chile.
Brain Res. 2005 Jul 19;1050(1-2):40-7. doi: 10.1016/j.brainres.2005.05.014.
In the present study, we have examined the physiological properties of synaptic currents mediated by GlyRs and GABAARs after culturing spinal neurons with a gephyrin antisense oligonucleotide. Application of gephyrin antisense, but not the sense, reduced the glycinergic mIPSC amplitude ( approximately 50%) and frequency ( approximately 85%), indicating the importance of gephyrin for GlyR anchoring at postsynaptic sites. On the other hand, the glycine-evoked current amplitude was unchanged indicating that functional GlyRs were still located in the extrasynaptic membrane. The analysis of the GABAergic transmission in the same neurons revealed approximately 70% reduction in the frequency of the GABAergic mIPSCs, without changes in the amplitude. Interestingly, the modulation of remaining GABAAR-mediated synaptic events by zinc and diazepam was significantly altered by the antisense. These results indicate that gephyrin is required for the membrane insertion/stabilization of the GABAAR gamma2 subunit as well as for its subsequent localization in the postsynaptic membrane.
在本研究中，我们在用桥连蛋白反义寡核苷酸培养脊髓神经元后，检测了由甘氨酸受体（GlyRs）和γ-氨基丁酸A型受体（GABAARs）介导的突触电流的生理特性。应用桥连蛋白反义寡核苷酸而非正义寡核苷酸，可降低甘氨酸能微小抑制性突触后电流（mIPSC）的幅度（约50%）和频率（约85%），这表明桥连蛋白对于甘氨酸受体在突触后位点的锚定很重要。另一方面，甘氨酸诱发的电流幅度未变，这表明功能性甘氨酸受体仍位于突触外膜。对同一神经元中γ-氨基丁酸能传递的分析显示，γ-氨基丁酸能mIPSCs的频率降低了约70%，而幅度未变。有趣的是，锌和地西泮对剩余的γ-氨基丁酸A型受体介导的突触事件的调节因反义寡核苷酸而发生了显著改变。这些结果表明，桥连蛋白对于γ-氨基丁酸A型受体γ2亚基的膜插入/稳定以及其随后在突触后膜中的定位是必需的。
Zotero 插件