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5- 羟色胺和/ 或pH 值的变化对大鼠舌下神经元漏钾电流的调制作用

徐雪峰, 蔡浩然, 李琳, 陈一凡, 张成, 王广发^*

北京大学第一医院1 呼吸内科；2 中心实验室，北京 100034

摘要

克隆的TWIK相关酸敏感型钾通道1 (TWIK-related acid-sensitive K+ channel, TASK-1)对生理范围的pH 值变化较为敏感 (pK~7.4)。最近在多种脑干运动神经元上发现了TASK-1 样通道，主要功能为编码背景性漏钾电流(TASK-1-like current)。本 文旨在研究舌下神经元漏钾电流的特性，以及5- 羟色胺(5-HT)和/ 或灌流液pH 值的变化对该电流的影响及其可能的机制。以 出生后7~8 d 的Sprague-Dawley (SD)大鼠为研究对象，应用活脑片技术获取大鼠舌下神经核细胞，利用脑片全细胞膜片钳技 术记录并分析运动神经元漏钾电流和超极化激活的阳离子电流(hyperpolarization-activated cationic current, Ih)。结果显示，漏 钾电流和Ih 可以被pH 6.0 的酸性人工脑脊液(artificial cerebrospinal fluid, ACSF)所抑制，亦可被pH 8.5 的碱性ACSF 所激活。10 μmol/L 5-HT 可显著抑制漏钾电流和Ih，并可使舌下神经元去极化，诱发阈下震荡和/ 或动作电位。给予5-HT2 受体拮抗剂 Ketanserine，可以拮抗酸性ACSF 对漏钾电流和Ih 的抑制作用。以上结果表明，酸性ACSF 对漏钾电流和Ih 的调制作用可能 是通过5-HT2 受体介导的。

关键词： 漏钾电流; 超极化激活电流; 膜片钳技术; 运动神经元; 5 - 羟色胺

分类号：Q421；Q426；R56；R332.3

Modulation of leak K+ channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value

XU Xue-Feng, TSAI Hao-Jan, LI Lin, CHEN Yi Fan, ZHANG Cheng, WANG Guang-Fa^*

Department of Pulmonary Medicine and Central Laboratory of Peking University First Hospital, Beijing 100034, China

Abstract

The cloned TWIK-related acid-sensitive K+ channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K+ conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K+ current (TASK-1-like current) and hyperpolarization-activated cationic current (Ih) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 μmol/L) significantly inhibited both leak K+ current and Ih with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT2 receptor, reversed or reduced the inhibitory effect of acidified solution on leak K+ current and Ih. The results suggest that 5-HT2 receptors mediate the effects of acidified media on leak K+ current and Ih in hypoglossal motoneurons.

Key words: potassium channel, leak; hyperpolarization-activated current; patch clamp techniques; motoneurons; serotonin

收稿日期：2009-04-10　　录用日期：2009-05-20

通讯作者：王广发　　E-mail: wangguangfa@hotmail.com

引用本文：

徐雪峰, 蔡浩然, 李琳, 陈一凡, 张成, 王广发. 5- 羟色胺和/ 或pH 值的变化对大鼠舌下神经元漏钾电流的调制作用[J]. 生理学报 2009; 61 (4): 305-316.

XU Xue-Feng, TSAI Hao-Jan, LI Lin, CHEN Yi Fan, ZHANG Cheng, WANG Guang-Fa. Modulation of leak K+ channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value. Acta Physiol Sin 2009; 61 (4): 305-316 (in Chinese with English abstract).