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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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Citing This Article：

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).