King A E, Liu X H
Department of Physiology, University of Leeds, U.K.
Neuropharmacology. 1996;35(12):1673-80. doi: 10.1016/s0028-3908(96)00140-2.
A dual action of selective metabotropic glutamate receptor agonists on neuronal excitability and dorsal root-evoked excitatory (DR-EPSPs) and inhibitory (DR-IPSPs) neurotransmission is described for immature rat ventral horn neurons in vitro. Trans-1-Aminocyclopentane-1,3 -dicarboxylate (trans-ACPD), its stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD) and (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG-1) produced a concentration-related and alpha-methyl-4 -carboxyphenylglycine (MCPG)-sensitive depolarisation. An (1S,3R)-ACPD- or L-CCG-1-induced increase in intrinsic neuronal excitability was apparently independent of the depolarisation and was observed as (a) a fall in the threshold current required to elicit regenerative excitation and (b) an increased number of spikes to a fixed amplitude step depolarisation. The spike after-hyperpolarisation (AHP) duration and amplitude were reduced, suggesting an mGluR agonist action on potassium channels. Synaptic responses were depressed by the mGluR agonists. (1S,3R)-ACPD or L-CCG-1 reduced the mean +/- S.E.M. peak amplitude of a subthreshold EPSP elicited by low-intensity stimuli likely to recruit only low-threshold sensory afferents. The peak amplitude of longer-latency EPSPs elicited by higher-intensity stimuli likely to recruit high-threshold afferents in addition was attenuated. (1S,3R)-ACPD- or L-CCG-1 reduced the peak amplitude of an IPSP evoked by dorsal root stimulation. These effects on synaptic transmission were likely to be due to the combined activation of postsynaptic and presynaptic metabotropic glutamate receptors. The implications of these data for the physiological role of spinal mGluRs is discussed.
本文描述了选择性代谢型谷氨酸受体激动剂对体外培养的未成熟大鼠腹角神经元的神经元兴奋性以及背根诱发的兴奋性（DR-EPSPs）和抑制性（DR-IPSPs）神经传递的双重作用。反式-1-氨基环戊烷-1,3-二羧酸（反式-ACPD）、其立体异构体（1S,3R）-1-氨基环戊烷-1,3-二羧酸（（1S,3R）-ACPD）和（2S,3S,4S）-α-（羧基环丙基）-甘氨酸（L-CCG-1）产生了浓度相关的、对α-甲基-4-羧基苯甘氨酸（MCPG）敏感的去极化。（1S,3R）-ACPD或L-CCG-1诱导的神经元内在兴奋性增加显然与去极化无关，表现为：（a）引发再生性兴奋所需的阈电流降低；（b）对固定幅度的阶跃去极化产生的峰电位数量增加。峰电位后超极化（AHP）的持续时间和幅度减小，提示代谢型谷氨酸受体激动剂对钾通道有作用。代谢型谷氨酸受体激动剂抑制突触反应。（1S,3R）-ACPD或L-CCG-1降低了低强度刺激（可能仅募集低阈值感觉传入纤维）诱发的阈下EPSP的平均±标准误峰值幅度。此外，高强度刺激（可能募集高阈值传入纤维）诱发的潜伏期较长的EPSP的峰值幅度也减弱。（1S,3R）-ACPD或L-CCG-1降低了背根刺激诱发的IPSP的峰值幅度。这些对突触传递的作用可能是由于突触后和突触前代谢型谷氨酸受体的联合激活。本文讨论了这些数据对脊髓代谢型谷氨酸受体生理作用的意义。
