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不同信号分子参与M胆碱能受体激动剂对不同胚胎发育阶段小鼠心肌细胞起搏电流的调控

宋元龙, 唐明, 刘长金, 梁华敏, 高琳琳, 席姣娅, 胡新武, 骆红艳, Hescheler Jürgen

武汉华中科技大学同济医学院生理系.湖北，武汉 430030；德国科隆大学神经生理研究所 D-50931

摘要

应用全细胞膜片钳技术，研究了M 胆碱能对不同孕期的胚胎小鼠心肌细胞的起搏电流（I_(f)）的调节。 我们发现，在胚胎发育的早期阶段，M胆碱能受体激动剂(muscarinic agonist carbachol,CCh) 明显抑制I_(f)，但在胚胎发育的晚期阶段，CCh对I_(f)的抑制作用消失。腺苷酸环化酶（adeinylate cyclase, AC）激动剂毛喉素Forskolin和非选择性磷酸二酯酶（PDE）抑制剂IBMX均可增强发育的早期阶段和晚期阶段的I_(f)。但有趣的是，尽管Forskolin和IBMX可增加基础I_(f)，它们对CCh抑制的I_(f)的作用却大不相同。在胚胎发育的早期阶段，Forskolin不能拮抗CCh对I_(f)的抑制作用，但IBMX可以。在发育的中期阶段Forskolin可以拮抗CCh的抑制作用，但IBMX不可以。因此，我们推断，CCh可能是通过调控细胞内的cAMP水平来调节I_(f)的。但是在胚胎发育的早期阶段和中期阶段，CCh是通过不同的信号转导通路来实现对胞内cAMP水平调控。在发育的早期阶段CCh主要是通过增强PDE的活性，加速cAMP的降解而实现对I_(f)的调控。而在发育的中期阶段CCh则主要通过与AC耦联，抑制其活性，通过减慢cAMP的合成而实现对I_(f)的调控。

关键词： M胆碱能调控; 膜片钳; 起搏电流

Different signal molecules involved in the muscarinic modulation of pacemaker current I_(f) on the heart of mouse embryo in different developmental stages

Song Yuanlong, Tang Ming, Liu Changjin, Liang Huamin, Gao Linlin, Xi Jiaoya, Hu Xinwu, Luo Hongyan, Heschelere J Jürgen

Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology.Wuhan 430030,Hubei

Abstract

We isolated mouse embryonic cardiomyocytes derived from timed-pregnant females at different periods and used patch-clamp technique to investigate the muscarinic cholinergic modulation of pacemaker current I_(f) in different developmental stages. In early development stage (EDS), muscarinic agonist carbachol (CCh) significantly decreased the magnitude of the pacemaker current I_(f) but without effect in late development stage (LDS). Forskolin (a direct adenylate cyclase activator ) and IBMX (a non-selective phosphodiesterase inhibitor ) increased I_(f) in both EDS and LDS cells. Interestingly, although both forskolin and IBMX increased basal I_(f) , their effects on CCh-inhibited I_(f) were different. Forskolin did not reverse the inhibitory action of CCh until intermediate development stage (IDS). In contrast, IBMX reversed the inhibitory action of CCh on I_(f) in EDS but not in IDS. It is suggested that a decrease in intracellular cAMP is a possible mechanism for CCh to modulate I_(f) ; During the EDS and IDS CCh controls the cytoplasmic cAMP level by different pathways: In EDS, CCh modulates I_(f) possibly by activating PDE which accelerates the breakdown of cAMP, but in IDS possibly by inhibiting adenylate cyclase (AC) which then reduces the synthesis of cAMP.

Key words: Muscarinic cholinergic modulation;patch clamp;Pacemaker current

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引用本文：

宋元龙, 唐明, 刘长金, 梁华敏, 高琳琳, 席姣娅, 胡新武, 骆红艳, Hescheler Jürgen . 不同信号分子参与M胆碱能受体激动剂对不同胚胎发育阶段小鼠心肌细胞起搏电流的调控[J]. 生理学报 2005; 57 (1): .

Song Yuanlong, Tang Ming, Liu Changjin, Liang Huamin, Gao Linlin, Xi Jiaoya, Hu Xinwu, Luo Hongyan, Heschelere J Jürgen . Different signal molecules involved in the muscarinic modulation of pacemaker current I_(f) on the heart of mouse embryo in different developmental stages. Acta Physiol Sin 2005; 57 (1): (in Chinese with English abstract).