general anesthetics modulation of GABAA receptor single-channnel currents

全身麻醉药对 GABAA 受体单通道电流的调节

• 批准号: 15591662
• 负责人: KITAMURA Akira
• 金额: $ 2.11万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591662/
• 关键词: general anesthetics; mechanism; patch clamp; ion channel; GABA; シングルチャネルレコーディング; シナプス伝達

Halothane and propofol enhance the activity of the GABAA system, which one of the most important systems in the mechanism of anesthesia. To determine whether halothane and propofol enhance GABAergic responses by the same mechanism, we performed single-channel patch-clamp experiments with rat cortical neurons in primary culture. Each of the open-time and closed-time distributions of GABAA receptor single channels was expressed by a sum of fast and slow time constants. Neither halothane nor propofol changed the single-channel conductance. Halothane increased the probability of the channel being open via a prolongation of the slow phase of open time, whereas propofol increased the channel open probability via a shortening of the slow phase of closed time. Thus, although both halothane and propofol augmented the channel open probability, thereby causing an increase in charge transfer during inhibitory transmitter action, they acted by different mechanisms.

氟烷和异丙酚增强GABAA系统的活性，GABAA系统是麻醉机制中最重要的系统之一。为了确定氟烷和异丙酚是否通过相同的机制增强GABA能反应，我们对原代培养的大鼠皮质神经元进行了单通道膜片钳实验。GABAA受体单通道的开放时间和关闭时间分布由快时间常数和慢时间常数之和表示。氟烷和异丙酚均不改变单通道电导。氟烷通过延长慢相开放时间增加通道开放概率，而异丙酚通过缩短慢相关闭时间增加通道开放概率。因此，虽然氟烷和异丙酚都增加了通道开放的概率，从而导致在抑制递质作用过程中电荷转移增加，但它们的作用机制不同。

项目成果

Halothane modulates NMDA and non-NMDA excitatory synaptic transmission in rat cortical neurons.

氟烷调节大鼠皮质神经元中的 NMDA 和非 NMDA 兴奋性突触传递。

• 发表时间: 2005
• 期刊: J Anesth 19(1)
• 作者: Kitamura A;Sato R;Sakamoto A;Ogawa R
• 通讯作者: Ogawa R

Halothane and propofol modulation of GABAA receptor single channel currents

氟烷和丙泊酚对 GABAA 受体单通道电流的调节

• 发表时间: 2004
• 期刊: Anesthesia and Analgesia 99
• 作者: Kitamura A;Sato R;Marszalec W;Yeh J;Ogawa R;Narahashi T
• 通讯作者: Narahashi T

Kitamura A, Manszalec W, Yeh JZ, Narahashi T: "Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons"J Pharmacol Exp Ther. 304・1. 162-171 (2003)

Kitamura A、Manszalec W、Yeh JZ、Narahashi T：“氟烷和异丙酚对大鼠皮质神经元的兴奋性和抑制性突触传递的影响”J Pharmacol Exp Ther 304・1（2003）。