Park Yun-Kyung, Galik Jan, Ryu Pan Dong, Randic Mirjana
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011-1250, USA.
Neurosci Lett. 2004 May 6;361(1-3):220-4. doi: 10.1016/j.neulet.2003.12.075.
The activation of group I metabotropic glutamate receptors (mGluRs) produces a long-term potentiation of sensory transmission in the substantia gelatinosa (SG) region of the spinal cord (Prog. Brain Res. 129 (2000) 115). The mechanism(s) responsible for the induction of this potentiation is not known. Using rat spinal cord slice preparation and patch-clamp recordings, here we show, that the activation of the group I mGluRs by (S)-3,5-dihydroxyphenylglycine (DHPG, 1 microM), the mGluR1/5 agonist, increased the frequency of both activity-dependent spontaneous EPSCs, and activity-independent miniature EPSCs (mEPSCs). However, DHPG did not affect amplitude of mEPSCs. The effects of DHPG were not seen in the presence of the preferential mGluR1 antagonist CPCCOEt (10 microM). On the other hand, 2-methyl-6-(phenylethynyl)-pyridine (10 microM), a selective mGluR5 antagonist, blocked the DHPG facilitation present during the wash-out of the drug. This novel facilitating effect of the group I mGluR activation on glutamate release is the first report of a direct facilitatory action of both mGluR1 and mGluR5 subtypes on sensory transmission in the spinal cord SG region. These results indicate the potential contribution of synaptic activation of these facilitatory autoreceptors in plasticity of primary afferent neurotransmission.
I 型代谢型谷氨酸受体(mGluRs)的激活可在脊髓胶状质(SG)区域产生感觉传递的长期增强(《脑研究进展》129卷(2000年)第115页)。导致这种增强的诱导机制尚不清楚。利用大鼠脊髓切片标本和膜片钳记录,我们在此表明,mGluR1/5激动剂(S)-3,5-二羟基苯甘氨酸(DHPG,1微摩尔)激活I型mGluRs,增加了活动依赖性自发兴奋性突触后电流(EPSCs)和非活动依赖性微小兴奋性突触后电流(mEPSCs)的频率。然而,DHPG并不影响mEPSCs的幅度。在存在优先mGluR1拮抗剂CPCCOEt(10微摩尔)的情况下,未观察到DHPG的作用。另一方面,选择性mGluR5拮抗剂2-甲基-6-(苯乙炔基)吡啶(10微摩尔)阻断了药物洗脱过程中存在的DHPG促进作用。I型mGluR激活对谷氨酸释放的这种新型促进作用是mGluR1和mGluR5亚型对脊髓SG区域感觉传递的直接促进作用的首次报道。这些结果表明这些促进性自身受体的突触激活在初级传入神经传递可塑性中的潜在作用。