Wang Xin
Departments of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA.
Anesth Analg. 2009 Jan;108(1):134-41. doi: 10.1213/ane.0b013e31818f871c.
Isoflurane is one of the most commonly used volatile anesthetics, yet the cardiorespiratory depression that occurs with its use remains poorly understood. In this study, the author examined isoflurane modulation of postsynaptic gamma-aminobutyric acid (GABA) receptors in parasympathetic cardiac vagal neurons (CVNs) and alterations of GABAergic function by targeting nicotinic acetylcholine receptors on GABAergic presynaptic terminals.
Rhythmic inspiratory-related activity was recorded from the hypoglossal rootlet of 800 microm medullary sections. CVNs were identified by retrograde fluorescent labeling, and GABAergic neurotransmission to CVNs were examined using patch-clamp electrophysiological techniques.
Isoflurane at concentrations of >50 microM significantly suppressed inspiratory bursting frequency, amplitude, and duration. Isoflurane dose-dependently decreased the frequency and increased the decay time of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) in CVNs. To test whether the inhibition of GABAergic activity to CVNs was mediated by presynaptic nicotinic receptors, the nicotinic antagonist, dihydro-beta-erythroidine in an alpha(4)beta(2)-selective concentration (3 microM), was used. Dihydro-beta-erythroidine (3 microM) prevented the isoflurane-evoked depression of spontaneous GABAergic IPSC frequency, yet isoflurane still increased the IPSC decay time.
These results suggest clinically relevant concentrations of isoflurane inhibit brainstem respiratory rhythmogenesis, prolong inhibitory GABAergic postsynaptic currents and reduce GABA activity in CVNs. The decrease of GABAergic IPSCs frequency is dependent upon inhibition of presynaptic alpha(4)beta(2) nicotinic receptors.
异氟烷是最常用的挥发性麻醉剂之一，但其使用过程中出现的心肺抑制仍未得到充分理解。在本研究中，作者研究了异氟烷对副交感神经心脏迷走神经元（CVNs）中突触后γ-氨基丁酸（GABA）受体的调节作用，以及通过靶向GABA能突触前终末上的烟碱型乙酰胆碱受体对GABA能功能的改变。
从800微米延髓切片的舌下神经根记录有节律的吸气相关活动。通过逆行荧光标记鉴定CVNs，并使用膜片钳电生理技术检查向CVNs的GABA能神经传递。
浓度>50微摩尔的异氟烷显著抑制吸气爆发频率、幅度和持续时间。异氟烷剂量依赖性地降低了CVNs中自发性GABA能抑制性突触后电流（IPSCs）的频率并增加了其衰减时间。为了测试对CVNs的GABA能活性的抑制是否由突触前烟碱型受体介导，使用了α(4)β(2)选择性浓度（3微摩尔）的烟碱拮抗剂二氢-β-刺桐碱。二氢-β-刺桐碱（3微摩尔）阻止了异氟烷诱发的自发性GABA能IPSC频率的降低，但异氟烷仍增加了IPSC衰减时间。
这些结果表明，临床相关浓度的异氟烷抑制脑干呼吸节律发生，延长抑制性GABA能突触后电流并降低CVNs中的GABA活性。GABA能IPSCs频率的降低取决于对突触前α(4)β(2)烟碱型受体的抑制。
