Drew Geoffrey M, Vaughan Christopher W
Pain Management Research Institute, Northern Clinical School, Royal North Shore Hospital, E25, University of Sydney, Sydney, NSW 2006, Australia.
Neuropharmacology. 2004 Jun;46(7):927-34. doi: 10.1016/j.neuropharm.2004.01.015.
The effect of metabotropic glutamate receptor (mGluR) activation on GABAergic synaptic transmission in rat periaqueductal grey (PAG) neurons was examined using whole-cell patch-clamp recordings in brain slices. The selective groups I, II and III mGluR agonists DHPG (10-30 microM), DCG-IV (1-3 microM) and L-AP4 (10-30 microM) inhibited electrically evoked GABA(A) mediated inhibitory postsynaptic currents (IPSCs) in all PAG neurons tested. DCG-IV and L-AP4 also reduced the frequency of spontaneous IPSCs, while DHPG produced both increases and decreases in spontaneous IPSC frequency in a dose dependent manner. In the presence of TTX, DHPG, DCG-IV and L-AP4 all reduced the frequency of spontaneous miniature IPSCs, but had no effect on their amplitudes. The DHPG, DCG-IV and L-AP4 effects on miniature IPSCs were dose dependent (EC(50)s=1.4, 0.055 and 0.52 microM, respectively) and were reduced by the selective mGluR antagonists MCPG, EGLU and MSOP, respectively. These results indicate that GABAergic synaptic transmission within the PAG is reduced by groups I, II and III mGluR activation via a presynaptic mechanism and is increased by group I mGluR activation via an action potential dependent mechanism. The finding of convergent groups I, II and III mGluR-mediated inhibition of synaptic transmission is novel and indicates that all groups of mGluRs have the potential to modulate the constellation of analgesic, behavioural and autonomic functions within the PAG.
采用脑片全细胞膜片钳记录技术，研究了代谢型谷氨酸受体（mGluR）激活对大鼠中脑导水管周围灰质（PAG）神经元GABA能突触传递的影响。选择性的I、II和III组mGluR激动剂DHPG（10 - 30微摩尔）、DCG - IV（1 - 3微摩尔）和L - AP4（10 - 30微摩尔）抑制了所有受试PAG神经元中电诱发的GABA(A)介导的抑制性突触后电流（IPSCs）。DCG - IV和L - AP4也降低了自发性IPSCs的频率，而DHPG则以剂量依赖的方式使自发性IPSC频率增加和降低。在存在河豚毒素（TTX）的情况下，DHPG、DCG - IV和L - AP4均降低了自发性微小IPSCs的频率，但对其幅度没有影响。DHPG、DCG - IV和L - AP4对微小IPSCs的作用呈剂量依赖性（EC(50)分别为1.4、0.055和0.52微摩尔），并分别被选择性mGluR拮抗剂MCPG、EGLU和MSOP所减弱。这些结果表明，I、II和III组mGluR激活通过突触前机制降低了PAG内的GABA能突触传递，而I组mGluR激活通过动作电位依赖性机制增加了GABA能突触传递。I、II和III组mGluR介导的对突触传递的汇聚性抑制这一发现是新颖的，表明所有组的mGluRs都有可能调节PAG内的镇痛、行为和自主神经功能。
