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内源性大麻素物质对家兔窦房结自律细胞动作电位的抑制作用

张娇, 王三怡, 周京京, 魏燕, 李茜, 杨晶, 张翼^*

河北医科大学生理学研究室，石家庄 050017

摘要

内源性大麻素物质(endocannabinoid anandamde, AEA)可对抗缺血/再灌注所致心脏损伤和心律失常，但其电生理机制尚未完全明了。本文旨在利用细胞内微电极记录方法观察AEA对家兔窦房结自律细胞动作电位的影响，并探讨其机制。采用新西兰大白兔制备离体窦房结标本并记录动作电位，通过累计给药法给予窦房结标本不同浓度(1、10、100、200和500 nmol/L)的AEA处理，部分标本在AEA (200 nmol/L)处理前，分别给予大麻素1型(CB1)受体阻断剂AM251、大麻素2型(CB2)受体阻断剂AM630、非特异性K+通道阻滞剂tetraethylammonium (TEA)和NO合酶抑制剂L-nitro-arginine methylester (L-NAME)预处理。结果显示：(1) AEA (100、200和500 nmol/L)可缩短家兔窦房结自律细胞的动作电位时程，降低动作电位幅度(P < 0.05)；(2) AM251可消除AEA缩短动作电位时程的作用，而AM630对此无影响；(3) TEA和L-NAME对AEA的作用无影响。结果提示，AEA可通过CB1受体降低家兔窦房结自律细胞动作电位幅度、缩短动作电位时程，此作用可能通过阻断Ca2+通道所实现，与K+通道及NO无关。

关键词： 内源性大麻素物质; 动作电位; 大麻素1型受体; 大麻素2型受体; 窦房结; 家兔

分类号：Q463; R331.3

Inhibitory effects of endocannabinoid on the action potential of pacemaker cells in sinoatrial nodes of rabbits

ZHANG Jiao, WANG San-Yi, ZHOU Jing-Jing, WEI Yan, LI Qian, YANG Jing, ZHANG Yi^*

Department of Physiology, Hebei Medical University, Shijiazhuang 050017

Abstract

Endocannabinoid anandamide (AEA) has protective effect on the heart against ischemia/reperfusion injury and arrhythmia, but the electrophysiological mechanism is unclear yet. In this study, the sinoatrial node (SAN) samples from New Zealand rabbits were prepared, and intracellular recording technique was used to elucidate the effect of AEA on the action potential (AP) of SAN pacemaker cells of rabbits and the mechanism. Different concentrations of AEA (1, 10, 100, 200, 500 nmol/L) were applied cumulatively. For some SAN samples, cannabinoid type 1 (CB1) receptor antagonist AM251, cannabinoid type 2 (CB2) receptor antagonist AM630, potassium channel blocker tetraethylammonium (TEA) and nitric oxide (NO) synthase inhibitor L-nitro-arginine methylester (L-NAME) were used before AEA treatment, respectively. We found that: (1) AEA (100, 200 and 500 nmol/L) not only shortened AP duration (APD), but also decreased AP amplitude (APA) (P < 0.05). (2) AM251, but not AM630, abolished the effect of AEA on APD shortening. (3) TEA and L-NAME had no influence on the AEA effect. These findings suggest that anandamide can decrease APA and shorten APD in SAN pacemaker cells of rabbits, which may be mediated by activation of CB1 receptors, and is related to blockade of calcium channels but not potassium channels and NO.

Key words: anandamide; action potential; cannabinoid type 1 receptor; cannabinoid type 2 receptor; sinoatrial node; rabbit

收稿日期：2012-07-02　　录用日期：2012-10-31

通讯作者：张翼　　E-mail: zhyhenry@hotmail.com

引用本文：

张娇, 王三怡, 周京京, 魏燕, 李茜, 杨晶, 张翼. 内源性大麻素物质对家兔窦房结自律细胞动作电位的抑制作用[J]. 生理学报 2013; 65 (2): 129-134.

ZHANG Jiao, WANG San-Yi, ZHOU Jing-Jing, WEI Yan, LI Qian, YANG Jing, ZHANG Yi. Inhibitory effects of endocannabinoid on the action potential of pacemaker cells in sinoatrial nodes of rabbits. Acta Physiol Sin 2013; 65 (2): 129-134 (in Chinese with English abstract).