Kaneko Keisuke, Koyanagi Yuko, Oi Yoshiyuki, Kobayashi Masayuki
Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Department of Anesthesiology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Neuroscience. 2016 Dec 17;339:548-560. doi: 10.1016/j.neuroscience.2016.10.016. Epub 2016 Oct 13.
Propofol is a major intravenous anesthetic that facilitates GABA receptor-mediated inhibitory synaptic currents and modulates inward current (I), K, and voltage-gated Na currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation. We conducted multiple whole-cell patch-clamp recordings from pyramidal neurons and from GABAergic neurons, which were classified into fast-spiking (FS), low threshold spike (LTS), late-spiking (LS), and regular-spiking nonpyramidal (RSNP) neurons. We found that 100μM propofol hyperpolarized the resting membrane potential and decreased input resistance in all types of neurons tested. Propofol also potently suppressed, and in most cases eliminated, repetitive spike firing in all these neurons. However, the potency of the propofol-induced changes in membrane and firing properties is particularly prominent in pyramidal neurons. Using a low concentration of propofol clarified this tendency: 30μM propofol decreased the firing of pyramidal neurons but had little effect on GABAergic neurons. Pre-application of a GABA receptor antagonist, picrotoxin (100μM), diminished the propofol-induced suppression of neural activities in both pyramidal and FS neurons. These results suggest that GABAergic neurons, especially FS neurons, are less affected by propofol than are pyramidal neurons and that propofol-induced modulation of the intrinsic membrane properties and repetitive spike firing are principally mediated by GABA receptor-mediated tonic currents.
丙泊酚是一种主要的静脉麻醉剂，它能促进γ-氨基丁酸（GABA）受体介导的抑制性突触电流，并调节内向电流（I）、钾电流和电压门控钠电流。丙泊酚对离子电流的这种调节作用会改变皮质锥体神经元的固有膜特性和重复动作电位发放。然而，丙泊酚是否会调节这些在不同水平表达这些离子通道的GABA能神经元的电生理特性尚不清楚。本研究在大鼠岛叶皮质脑片标本中检测了丙泊酚对锥体神经元和GABA能神经元特性的调节是否存在差异。我们对锥体神经元和GABA能神经元进行了多次全细胞膜片钳记录，后者又分为快发放（FS）、低阈值发放（LTS）、晚发放（LS）和规则发放非锥体（RSNP）神经元。我们发现，100μM丙泊酚使所有测试类型神经元的静息膜电位超极化，并降低了输入电阻。丙泊酚还能有效抑制并在大多数情况下消除所有这些神经元的重复动作电位发放。然而，丙泊酚引起的膜和发放特性变化的效力在锥体神经元中尤为显著。使用低浓度丙泊酚明确了这种趋势：30μM丙泊酚降低了锥体神经元的发放，但对GABA能神经元影响很小。预先应用GABA受体拮抗剂印防己毒素（100μM）可减弱丙泊酚对锥体神经元和FS神经元神经活动的抑制作用。这些结果表明，与锥体神经元相比，GABA能神经元尤其是FS神经元受丙泊酚的影响较小，并且丙泊酚对固有膜特性和重复动作电位发放的调节主要由GABA受体介导的强直电流介导。
