氟烷可增强A型γ-氨基丁酸受体功能，但在去大脑犬模型中，它不会改变吸气前运动神经元的整体抑制作用。

Halothane enhances gamma-aminobutyric acid receptor type A function but does not change overall inhibition in inspiratory premotor neurons in a decerebrate dog model.

作者信息

Stucke Astrid G, Zuperku Edward J, Tonkovic-Capin Viseslav, Krolo Mirko, Hopp Francis A, Kampine John P, Stuth Eckehard A E

机构信息

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.

出版信息

Anesthesiology. 2003 Dec;99(6):1303-12. doi: 10.1097/00000542-200312000-00011.

DOI:10.1097/00000542-200312000-00011

PMID:14639142

Abstract

BACKGROUND

Inspiratory premotor neurons in the caudal ventral medulla relay excitatory drive to phrenic and inspiratory intercostal motoneurons in the spinal cord. These neurons are subject to tonic gamma-aminobutyric acid type A (GABA(A))-mediated (GABA(A)ergic) inhibition. In a previous study, 1 minimum alveolar concentration (MAC) halothane depressed overall glutamatergic excitatory drive but did not change overall inhibitory drive to the neurons. This study investigated in further detail the effects of halothane on GABA(A)ergic inhibition by examining postsynaptic GABA(A) receptor activity in these neurons.

METHODS

Studies were performed in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 MAC halothane on extracellularly recorded neuronal activity was measured during localized picoejection of the GABA(A) receptor antagonist bicuculline and the GABA(A) agonist muscimol. Complete blockade of GABAergic inhibition by bicuculline allowed estimation of the prevailing overall inhibition of the neuron. The neuronal response to muscimol was used to assess the anesthetic effect on the postsynaptic GABA(A) receptor function.

RESULTS

One minimum alveolar concentration halothane depressed the spontaneous activity of 19 inspiratory premotor neurons by 22.9 +/- 29.1% (mean +/- SD; P < 0.01). Overall excitatory drive was depressed 23.6 +/- 16.9% (P < 0.001). Overall GABAergic inhibition was not changed (+8.7 +/- 27.5%; P = 0.295), but the postsynaptic GABA(A) receptor function was increased by 110.3 +/- 97.5% (P < 0.001).

CONCLUSION

One minimum alveolar concentration halothane greatly enhanced GABA(A) receptor function on inspiratory premotor neurons but did not change overall synaptic inhibition, indicating that the presynaptic inhibitory input was reduced. Therefore, the anesthetic depression of spontaneous inspiratory premotor neuronal activity in the intact brainstem respiratory network is mainly due to a decrease in overall glutamatergic excitation.

摘要

背景

延髓尾端腹侧的吸气前运动神经元将兴奋性冲动传递至脊髓中的膈神经运动神经元和吸气性肋间运动神经元。这些神经元受到持续性γ-氨基丁酸A型（GABA(A)）介导的（GABA(A)能）抑制作用。在之前的一项研究中，1个最低肺泡浓度（MAC）的氟烷降低了整体谷氨酸能兴奋性冲动，但并未改变对这些神经元的整体抑制性冲动。本研究通过检测这些神经元的突触后GABA(A)受体活性，进一步详细探讨了氟烷对GABA(A)能抑制作用的影响。

方法

在高碳酸血症性高氧状态下，对去大脑、切断迷走神经、麻痹并机械通气的犬进行研究。在局部微量注射GABA(A)受体拮抗剂荷包牡丹碱和GABA(A)激动剂蝇蕈醇期间，测量1个MAC氟烷对细胞外记录的神经元活动的影响。荷包牡丹碱完全阻断GABA能抑制作用，从而可以评估神经元当前的整体抑制情况。神经元对蝇蕈醇的反应用于评估麻醉对突触后GABA(A)受体功能的影响。

结果

1个MAC氟烷使19个吸气前运动神经元的自发活动降低了22.9±29.1%（平均值±标准差；P<0.01）。整体兴奋性冲动降低了23.6±16.9%（P<0.001）。整体GABA能抑制作用未发生改变（+8.7±27.5%；P=0.295），但突触后GABA(A)受体功能增加了110.3±97.5%（P<0.001）。