Seoul National University Hospital, Daehakro 101, Jongno-gu, Seoul, Korea.
Anesth Analg. 2011 May;112(5):1096-102. doi: 10.1213/ANE.0b013e31820fcc3e. Epub 2011 Apr 7.
The gamma aminobutyric acid type A (GABA(A)) receptor is a prime target of many anesthetics, including midazolam and propofol. Although these anesthetics have sedative and hypnotic properties by enhancing GABA(A) receptor activity, their interactions at the GABA(A) receptors have not been explored. We investigated the interaction of midazolam and propofol with α(1)β(2)γ(2)L and α(1)β(2)γ(2)S GABA(A) receptors.
Using the whole-cell patch clamp technique, we tested the effects of midazolam and propofol on GABA-induced currents in human embryonic kidney 293 T cells transfected with α(1)β(2)γ(2)L and α(1)β(2)γ(2)S GABA(A) receptors.
Midazolam and propofol on their own enhanced the amplitude of GABA(A) receptor responses in a dose-dependent manner, and they had additive effects on α(1)β(2)γ(2)S GABA(A) receptors, but not on α(1)β(2)γ(2)L GABA(A) receptors. However, additive interactions of midazolam and propofol on the α(1)β(2)γ(2)L GABA(A) receptors were observed when protein kinase C was inhibited.
The interaction between midazolam and propofol is affected by receptor subtype, and protein kinase phosphorylation influences their interaction on the α(1)β(2)γ(2)L receptor.
γ-氨基丁酸 A 型（GABA(A)) 受体是许多麻醉剂的主要靶点，包括咪达唑仑和丙泊酚。虽然这些麻醉剂通过增强 GABA(A)受体活性具有镇静和催眠作用，但它们在 GABA(A)受体上的相互作用尚未得到探索。我们研究了咪达唑仑和丙泊酚与 α(1)β(2)γ(2)L 和 α(1)β(2)γ(2)S GABA(A)受体的相互作用。
使用全细胞膜片钳技术，我们测试了咪达唑仑和丙泊酚对转染有 α(1)β(2)γ(2)L 和 α(1)β(2)γ(2)S GABA(A)受体的人胚肾 293 T 细胞中 GABA 诱导电流的影响。
咪达唑仑和丙泊酚本身以剂量依赖的方式增强 GABA(A)受体反应的幅度，它们对 α(1)β(2)γ(2)S GABA(A)受体具有加性作用，但对 α(1)β(2)γ(2)L GABA(A)受体没有加性作用。然而，当蛋白激酶 C 被抑制时，咪达唑仑和丙泊酚对 α(1)β(2)γ(2)L GABA(A)受体的加性相互作用被观察到。
咪达唑仑和丙泊酚之间的相互作用受受体亚型的影响，蛋白激酶磷酸化影响它们在 α(1)β(2)γ(2)L 受体上的相互作用。
