Emri Z, Turner J P, Crunelli V
Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff, UK.
Neuroscience. 1996 Jun;72(3):689-98. doi: 10.1016/0306-4522(95)00590-0.
The presence and role of presynaptic GABA(B) receptors in the control of excitatory amino acid-medicated transmission were investigated (using sharp electrode recordings) in the rat dorsal lateral geniculate nucleus and ventrobasal thalamus in vitro by comparing the effects of the selective GABA(B) receptor agonist, (+ or -)-baclofen, and of two antagonists, CGP 35348 and 2-hydroxy-saclofen, on the excitatory postsynaptic potentials evoked in thalamocortical neurons by stimulation of the sensory afferents. Application of CGP 35348 alone blocked the GABA(B) receptor-mediated inhibitory postsynaptic potential evoked in the dorsal lateral geniculate nucleus by stimulation of the optic tract (n = 5), but had no effect on the resting membrane potential and input resistance of thalamocortical cells (n = 6). In contrast, 2-hydroxy-saclofen caused a hyperpolarization (6.9 + or - 0.5 mV, n = 10) and a decrease in the apparent input resistance (26.3 + or - 2.6%, n = 10). This effect of 2-hydroxy-saclofen was antagonized by CGP 35348. When bicuculline was present in the perfusion medium and following intracellular injection of QX 314, GABA(A) and GABA(B) receptors in the recorded neurons were blocked. Under this condition, application of baclofen decreased the amplitude of the medial lemniscus- and optic tract-evoked excitatory postsynaptic potentials in the two thalamic nuclei investigated. This effect was fully antagonized by CGP 35348 and only partially by 2-hydroxy-saclofen. CGP 35348 alone increased (19.3 + or - 4.3%, n = 5) and 2-hydroxy-saclofen alone decreased (29.9 + or - 8.6%, n = 5) the amplitude of the excitatory postsynaptic potential. This effect of 2-hydroxy-saclofen was not blocked by CGP 35348. These results indicate that presynaptic GABA(B) receptors are present on the terminals of the sensory afferents in the rat dorsal lateral geniculate nucleus and in the ventrobasal thalamus. These receptors are tonically activated by endogenous GABA, at least in vitro, and provide a negative control mechanism by which the excitatory amino acid-mediated transmission within these nuclei can be regulated. In contrast, the endogenous GABA level is not sufficient for a tonic activation of postsynaptic GABA(B) receptors. Furthermore, these results indicate that 2-hydroxy-saclofen acts as a partial agonist on postsynaptic CGP 35348-sensitive GABA(B) receptors, and that, in addition to its antagonist action on presynaptic CGP 35348-sensitive GABA(B) receptors, it also has an effect on either presynaptic, CGP 35348-insensitive GABA(B) receptors and/or another presynaptic receptor type.
采用尖锐电极记录法，通过比较选择性γ-氨基丁酸B（GABA(B)）受体激动剂（±）巴氯芬以及两种拮抗剂CGP 35348和2-羟基巴氯芬对感觉传入刺激诱发的丘脑皮质神经元兴奋性突触后电位的影响，在体外研究大鼠背外侧膝状核和腹基底丘脑前突触GABA(B)受体的存在及其在兴奋性氨基酸介导的传递控制中的作用。单独应用CGP 35348可阻断视束刺激在背外侧膝状核诱发的GABA(B)受体介导的抑制性突触后电位（n = 5），但对丘脑皮质细胞的静息膜电位和输入电阻无影响（n = 6）。相反，2-羟基巴氯芬引起超极化（6.9±0.5 mV，n = 10）并使表观输入电阻降低（26.3±2.6%，n = 10）。CGP 35348可拮抗2-羟基巴氯芬的这种作用。当灌流液中存在荷包牡丹碱并在细胞内注射QX 314后，记录神经元中的GABA(A)和GABA(B)受体被阻断。在此条件下，应用巴氯芬可降低所研究的两个丘脑核团中内侧丘系和视束诱发的兴奋性突触后电位的幅度。这种作用可被CGP 35348完全拮抗，而仅被2-羟基巴氯芬部分拮抗。单独应用CGP 35348可使兴奋性突触后电位幅度增加（19.3±4.3%，n = 5），单独应用2-羟基巴氯芬则使其降低（29.9±8.6%，n = 5）。2-羟基巴氯芬的这种作用不能被CGP 35348阻断。这些结果表明，大鼠背外侧膝状核和腹基底丘脑感觉传入神经末梢存在前突触GABA(B)受体。这些受体至少在体外被内源性GABA持续激活，并提供一种负性控制机制，通过该机制可调节这些核团内兴奋性氨基酸介导的传递。相反，内源性GABA水平不足以持续激活突触后GABA(B)受体。此外，这些结果表明，2-羟基巴氯芬对突触后CGP 35348敏感的GABA(B)受体起部分激动剂作用，并且除了对突触前CGP 35348敏感的GABA(B)受体具有拮抗作用外，它还对突触前CGP 35348不敏感的GABA(B)受体和/或另一种突触前受体类型有影响。
