Zagorodnyuk Vladimir P, D'Antona Giuseppe, Brookes Simon J H, Costa Marcello
Department of Human Physiology, Centre for Neuroscience, Flinders University of South Australia, GPO Box 2100, Adelaide, South Australia, Australia.
Auton Neurosci. 2002 Nov 29;102(1-2):20-9. doi: 10.1016/s1566-0702(02)00183-2.
The effects of the GABAB-selective agonist baclofen were studied on guinea pig nodose ganglion neurones using grease gap and intracellular recording techniques, and on peripheral mechanosensitive endings in the guinea pig oesophagus and stomach with extracellular recordings. GABA dose-dependently reduced the amplitude of the compound action potential of C-type neurones (C spikes, EC50 = 30.9 microM), which was prevented by the GABAA antagonist bicuculline (10 microM). The GABAB agonist baclofen (1-300 microM) did not produce any significant effect on the amplitude of C spikes. In microelectrode studies, baclofen (100 microM) evoked hyperpolarisation (by 2.53 +/- 0.51 mV, n = 6, N = 5) in a subset of nodose neurones (6 out of 26, N = 18). In seven out of eight neurones (N = 8) with a slow after-hyperpolarisation following action potentials, baclofen significantly inhibited its amplitude by 19 +/- 4% (n = 7, p < 0.05). GABA (100 microM) evoked a depolarisation of 9.3 +/- 2.4 mV (10 nodose neurones, N = 9, p < 0.05) associated with a decrease in input impedance of 49 +/- 12% (N = 4, p < 0.05). Baclofen (100-200 microM) did not affect either spontaneous or stretch-evoked firing of distension-sensitive vagal mechanoreceptors of the guinea pig oesophagus and stomach but did inhibit mechanoreceptors in the ferret oesophagus. Antibodies to GABAB receptor 1a splice variants labelled most of the neurones and numerous fibres in the guinea pig nodose ganglion while antibodies to GABAB receptor 1b splice variants stained only nerve cell bodies. There were numerous nerve fibres showing GABAB receptor 1a- and 1b-like immunoreactivity in the myenteric plexus in the guinea pig oesophagus and stomach but not in anterogradely labelled extrinsic vagal nerve fibres. The result indicates that most guinea pig C-type nodose ganglion neurones have GABAB receptors on their cell bodies but their density on distension-sensitive peripheral endings is too low to allow modulation of mechanotransduction. There is a significant species-dependent difference in the expression of GABAB receptors on peripheral vagal mechanosensitive endings.
采用脂膜间隙法和细胞内记录技术，研究了GABAB选择性激动剂巴氯芬对豚鼠结状神经节神经元的作用；并采用细胞外记录法，研究了其对豚鼠食管和胃外周机械敏感末梢的作用。GABA能剂量依赖性地降低C型神经元复合动作电位的幅度（C波峰，EC50 = 30.9 microM），GABAA拮抗剂荷包牡丹碱（10 microM）可阻断此作用。GABAB激动剂巴氯芬（1 - 300 microM）对C波峰的幅度未产生任何显著影响。在微电极研究中，巴氯芬（100 microM）可使一部分结状神经元（26个中的6个，N = 18）发生超极化（超极化2.53±0.51 mV，n = 6，N = 5）。在8个动作电位后出现缓慢超极化的神经元中，有7个（N = 8），巴氯芬可使其幅度显著降低19±4%（n = 7，p < 0.05）。GABA（100 microM）可使9.3±2.4 mV的去极化（10个结状神经元，N = 9，p < 0.05），同时输入阻抗降低49±12%（N = 4，p < 0.05）。巴氯芬（100 - 200 microM）对豚鼠食管和胃扩张敏感的迷走机械感受器的自发放电或牵张诱发放电均无影响，但可抑制雪貂食管中的机械感受器。针对GABAB受体1a剪接变体的抗体标记了豚鼠结状神经节中的大多数神经元和许多纤维，而针对GABAB受体1b剪接变体的抗体仅对神经细胞体染色。在豚鼠食管和胃的肌间神经丛中有许多神经纤维显示出GABAB受体1a和1b样免疫反应性，但在顺行标记的迷走神经外纤维中则没有。结果表明，大多数豚鼠C型结状神经节神经元在其细胞体上有GABAB受体，但在扩张敏感的外周末梢上其密度过低，无法调节机械转导。外周迷走机械敏感末梢上GABAB受体的表达存在显著的种属依赖性差异。
