Sevoflurane enhances γ-aminobutyric acid type A receptor function and overall inhibition of inspiratory premotor neurons in a decerebrate dog model
Sevoflurane enhances γ-aminobutyric acid type A receptor function and overall inhibition of inspiratory premotor neurons in a decerebrate dog model
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DOI：
10.1097/00000542-200507000-00012
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发表时间：
2005-07-01
期刊：
影响因子：
8.8
通讯作者：
Stuth, EAE
中科院分区：
文献类型：
--
作者：
Stucke, AG;Zuperku, EJ;Stuth, EAE
背景资料：延髓尾侧腹侧的吸气运动前神经元将兴奋性驱动传递给脊髓的膈神经和吸气肋间运动神经元。这些神经元受到紧张性γ-氨基丁酸A型（GABA（A））能抑制。在先前的一项研究中，1最小肺泡浓度（MAC）的七氟烷抑制了对神经元的总体GABA能兴奋性驱动，并增强了对神经元的总体GABA（A）能抑制性驱动。本研究通过检查这些神经元中突触后GABAA受体活性，进一步详细研究了七氟烷对GABA（A）能抑制的影响。方法：在去大脑、迷走神经切断、瘫痪和机械通气的狗中进行了研究。在GABAA受体拮抗剂荷包牡丹碱和GABA（A）激动剂蝇蕈醇的局部微微喷射期间，测量了1 MAC七氟烷对细胞外记录的神经元活动的影响。通过荷包牡丹碱完全阻断GABA能抑制，可以估计神经元的普遍总体抑制。结果：1 MAC七氟醚可抑制21个吸气运动前神经元的自发活动，抑制率为32.6 ± 20.5%（P < 0.001）。总体兴奋性驱动降低17.9 ± 19.8%（P < 0.01）。总体GABA能抑制增强18.5 +/- 18.2%（P < 0.001），突触后GABA（A）受体功能增加184.4 ± 121.8%（n = 20; P < 0.001）。一个MAC的七氟醚极大地增强了GABA，受体功能的吸气运动前神经元和增加整体突触抑制，但在较小程度上，表明突触前抑制输入也减少。因此，1 MAC司维鲁烷在体内对自发吸气运动前神经元活动的麻醉抑制是由于对两种主要离子型突触神经递质系统的联合作用，即总体兴奋性兴奋降低和突触后GABAA受体功能强烈增强。
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))ergic inhibition. In a previous study, 1 minimum alveolar concentration (MAC) sevoflurane depressed overall glutamatergic excitatory drive and enhanced overall GABA(A)ergic inhibitory drive to the neurons. This study investigated in further detail the effects of sevoflurane on GABA(A)ergic inhibition by examining postsynaptic GABAA 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 sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the GABAA receptor antagonist bicuculline and the GABA(A) agonist muscimol. Complete blockade of GABAAergic 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 GABAA receptor function.Results: One MAC sevoflurane depressed the spontaneous activity of 21 inspiratory premotor neurons by (mean +/- SD) 32.6 +/- 20.5% (P < 0.001). Overall excitatory drive was depressed 17.9 +/- 19.8% (P < 0.01). Overall GABAAergic inhibition was enhanced by 18.5 +/- 18.2% (P < 0.001), and the postsynaptic GABA(A) receptor function was increased by 184.4 +/- 121.8% (n = 20; P < 0.001).Conclusion: One MAC sevoflurane greatly enhanced GABA, receptor function on inspiratory premotor neurons and increased overall synaptic inhibition but to a smaller extent, indicating that the presynaptic inhibitory input was also reduced. Therefore, die anesthetic depression of spontaneous inspiratory premotor neuronal activity by 1 MAC sevollurane in vivo is due to a combined effect on the two major ionotropic synaptic neurotransmitter systems with a decrease in overall glutamatergic excitation and a strong enhancement of postsynaptic GABAA receptor function.