Ferraro L, Beani L, Bianchi C, Tanganelli S
Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
Neurochem Int. 1997 Dec;31(6):795-800. doi: 10.1016/s0197-0186(97)00026-0.
In the present study we characterize the optimal experimental conditions under which to investigate the cholinergic regulation of endogenous electrically evoked gamma-aminobutyric acid (GABA) release from guinea pig cortical slices. Superfusion with the neuronal GABA reuptake inhibitor, SKF89976A (10 microM) caused cortical GABA release to be linearly correlated with the frequency of electrical stimulation (5, 10, 20 Hz). Electrically evoked GABA release (10 Hz) was tetrodotoxin-sensitive and Ca(2+)-dependent and was under GABAB autoreceptor control. Under these experimental conditions, acetylcholine (0.1-10 microM) and physostigmine (30 microM) decreased the electrically evoked GABA release while the M2 receptor antagonist AFDX-116 (0.01-0.1 microM) counteracted these effects. Similar results were also observed in a cortical synaptosomal preparation stimulated with K+ (10 mM). These findings demonstrate an inhibitory cholinergic regulation of electrically evoked GABA release via M2 receptors located on cortical GABAergic terminals.
在本研究中，我们确定了最佳实验条件，在此条件下可研究豚鼠皮质切片中内源性电诱发γ-氨基丁酸（GABA）释放的胆碱能调节。用神经元GABA再摄取抑制剂SKF89976A（10微摩尔）进行灌流，导致皮质GABA释放与电刺激频率（5、10、20赫兹）呈线性相关。电诱发的GABA释放（10赫兹）对河豚毒素敏感且依赖Ca(2+)，并受GABAB自受体控制。在这些实验条件下，乙酰胆碱（0.1 - 10微摩尔）和毒扁豆碱（30微摩尔）减少了电诱发的GABA释放，而M2受体拮抗剂AFDX - 116（0.01 - 0.1微摩尔）抵消了这些作用。在用K+（10毫摩尔）刺激的皮质突触体标本中也观察到了类似结果。这些发现表明，通过位于皮质GABA能终末的M2受体，胆碱能对电诱发的GABA释放具有抑制调节作用。
