挥发性麻醉药对海马中间神经元中GABAA受体介导的突触抑制的作用具有药物选择性。

Agent-selective effects of volatile anesthetics on GABAA receptor-mediated synaptic inhibition in hippocampal interneurons.

作者信息

Nishikawa K, MacIver M B

机构信息

C.V. Starr Laboratory of Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, New York 10021, USA.

出版信息

Anesthesiology. 2001 Feb;94(2):340-7. doi: 10.1097/00000542-200102000-00025.

DOI:10.1097/00000542-200102000-00025

PMID:11176100

Abstract

BACKGROUND

A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons.

METHODS

Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons.

RESULTS

Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics.

CONCLUSIONS

Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.

摘要

背景

相对少数的抑制性中间神经元能够控制海马体及其他皮质区域中大量锥体细胞的兴奋性和同步性。因此，中间神经元的麻醉调节可能对麻醉的维持起着重要作用。本研究的目的是比较挥发性麻醉药对大鼠海马体中间神经元抑制性突触后电流（IPSCs）的影响。

方法

采用全细胞膜片钳技术在大鼠海马体切片中视觉识别的中间神经元上记录药理学分离的γ-氨基丁酸A型（GABAA）受体介导的IPSCs。研究位于CA1区辐射层-分子层的神经元。比较了临床相关浓度（1.0倍大鼠最低肺泡浓度）的氟烷、恩氟烷、异氟烷和七氟烷对中间神经元中刺激诱发和自发性GABAA受体介导的IPSCs动力学的影响。

结果

氟烷（1.2体积%，约0.35 mmol/L）、恩氟烷（2.2体积%，约0.60 mmol/L）、异氟烷（1.4体积%，约0.50 mmol/L）和七氟烷（2.7体积%，约0.40 mmol/L）分别将诱发的IPSC幅度优先抑制至对照的79.8±9.3%（n = 5）、38.2±8.6%（n = 6）、52.4±8.4%（n = 5）和46.1±16.0%（n = 8）。此外，所有麻醉药均不同程度地将诱发的IPSCs的衰减时间常数延长至对照的290.1±33.2%、423.6±47.1%、277.0±32.2%和529±48.5%。所有麻醉药均增加了自发性IPSCs的频率（增加两倍至三倍）。因此，所有麻醉药均增强了突触连接的中间神经元之间由GABAA受体介导的总负电荷转移。