Department of Pharmacology and Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Department of Anesthesiology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Acta Pharmacol Sin. 2019 Jun;40(6):755-761. doi: 10.1038/s41401-018-0168-6. Epub 2018 Oct 26.
Propofol is an intravenous anesthetic that can active γ-aminobutyric acid A (GABA) receptors and generate sedative-hypnotic effects. Propofol has been widely applied clinically to achieve sedation comparable to sleep in humans. The basal forebrain (BF) is a brain region that plays an important role in sleep-wake regulation. Previous studies suggest that propofol affects the sleep-wake circuit via the BF; however, the mechanism remains elusive. In the current study we investigated the effects of propofol on the inherent properties of cholinergic neurons and their ability to convert excitatory inputs into spikes in mouse BF slices using whole-cell patch clamp recordings. Bath application of propofol (10 μM) significantly elevated the threshold potentials (Vts), decreased the number of spikes in response to a depolarizing current injection, and augmented the inter-spike intervals (ISIs), energy barrier (Vts-Vrs), and absolute refractory periods (ARPs). These effects were eliminated by co-application of a GABA receptor antagonist picrotoxin (50 μM). Altogether, our results reveal that propofol decreases the excitability of cholinergic neurons in mouse BF via GABA receptors.
异丙酚是一种静脉麻醉剂，可激活γ-氨基丁酸 A（GABA）受体并产生镇静催眠作用。异丙酚已广泛应用于临床，以实现与人类睡眠相当的镇静作用。基底前脑（BF）是在睡眠-觉醒调节中起重要作用的脑区。先前的研究表明，异丙酚通过 BF 影响睡眠-觉醒回路；然而，其机制仍不清楚。在本研究中，我们使用全细胞膜片钳记录研究了异丙酚对小鼠 BF 切片中胆碱能神经元固有特性及其将兴奋性输入转换为尖峰的能力的影响。异丙酚（10μM）的浴液应用显著提高了阈电位（Vts），减少了对去极化电流注射的反应中尖峰的数量，并增加了尖峰间隔（ISIs）、能量屏障（Vts-Vrs）和绝对不应期（ARPs）。这些作用通过共应用 GABA 受体拮抗剂荷包牡丹碱（50μM）而消除。总的来说，我们的结果表明，异丙酚通过 GABA 受体降低了小鼠 BF 中胆碱能神经元的兴奋性。
