Frumkes T E, Nelson R, Pflug R
Laboratory of Neurophysiology, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, USA.
Vis Neurosci. 1995 Jul-Aug;12(4):651-61. doi: 10.1017/s0952523800008944.
Putative GABAergic mechanisms were studied in the cat retina by exogenous application of the GABAA antagonists picrotoxin (PTX), native bicuculline (BCC), and bicuculline methyl bromide (BCC MeBr). When recording intracellular responses from horizontal cells (HCs) and amacrine cells as well as electroretinograms (ERGs), drugs were added to the perfusate used to maintain the isolated eyecup; when recording extracellular spikes from ganglion cells of anesthetized cats, drugs were introduced by iontophoretic injection. Both PTX and BCC MeBr had relatively little influence upon the response properties of HCs. In contrast, native BCC tended to decrease the amplitude of and to slow the photic response to light onset and both to quicken and to increase the amplitude of response to light offset; in the presence of native BCC, HC responses were dominated by a prominent spike-like "Off-overshoot." The influence of GABAA agonists upon HC responses was not blocked by GABAA antagonists. ERG b-wave amplitude was reduced both by PTX and by native BCC, but was not influenced by BCC MeBr. Latency (time to half-peak) was increased by low doses of native BCC, and to a lesser extent PTX but not BCC MeBr. Rod-amacrine On-transient responses were increased in amplitude by PTX. Extracellular recordings from On- and Off- X and Y ganglion cell types became considerably more transient with application of either PTX, native BCC, or BCC MeBr; this tendency was greater in Off-type ganglion cells. Collectively, these results strengthen conclusions from the previous paper suggesting that GABA serves to slow onset and offset kinetics of retinal neurons, making them more sustained and less phasic. They also suggest that in mammalian retina heterogeneous types of GABAA receptors exist, segregated into different zones: a distal zone, sensitive only to native BCC, a central zone sensitive to both native BCC and PTX, and a proximal zone sensitive to native BCC, BCC methyl halides (BCC MeH), and PTX. Only the proximal zone obeys conventional GABAA pharmacology.
通过外源应用γ-氨基丁酸A（GABAA）拮抗剂印防己毒素（PTX）、天然荷包牡丹碱（BCC）和荷包牡丹碱甲基溴（BCC MeBr），对猫视网膜中假定的γ-氨基丁酸能机制进行了研究。在记录水平细胞（HCs）和无长突细胞的细胞内反应以及视网膜电图（ERGs）时，将药物添加到用于维持离体眼球杯的灌注液中；在记录麻醉猫神经节细胞的细胞外尖峰时，通过离子电泳注射引入药物。PTX和BCC MeBr对HCs的反应特性影响相对较小。相比之下，天然BCC倾向于降低对光开始的光反应幅度并减慢其速度，同时加快并增加对光熄灭的反应幅度；在存在天然BCC的情况下，HC反应以突出的尖峰样“Off-过冲”为主导。GABAA激动剂对HC反应的影响未被GABAA拮抗剂阻断。PTX和天然BCC均降低了ERG b波幅度，但BCC MeBr对其无影响。低剂量的天然BCC增加了潜伏期（达到半峰的时间），PTX在较小程度上也有增加，但BCC MeBr没有。PTX增加了视杆无长突细胞的On-瞬态反应幅度。应用PTX、天然BCC或BCC MeBr后，来自On-和Off-X及Y神经节细胞类型的细胞外记录变得更加瞬态化；这种趋势在Off型神经节细胞中更明显。总体而言，这些结果强化了前一篇论文的结论表明γ-氨基丁酸有助于减慢视网膜神经元的起始和终止动力学，使其更具持续性且更少相位性。它们还表明在哺乳动物视网膜中存在异质性的GABAA受体类型，分为不同区域：一个仅对天然BCC敏感的远端区域，一个对天然BCC和PTX均敏感的中央区域，以及一个对天然BCC、BCC甲基卤化物（BCC MeH）和PTX敏感的近端区域。只有近端区域遵循传统的GABAA药理学。
