Different signal molecules involved in the muscarinic modulation of pacemaker current I(f) on the heart of mouse embryo in different developmental stages.
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 had no 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.
Song
Yuan-Long
YL
Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Tang
Ming
M
Liu
Chang-Jin
CJ
Liang
Hua-Min
HM
Gao
Lin-Lin
LL
Xi
Jiao-Ya
JY
Hu
Xin-Wu
XW
Luo
Hong-Yan
HY
Hescheler
Jurgen
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000196:embryology* / Q000502:physiology; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D010138:Pacemaker, Artificial; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011247:Pregnancy; D011976:Receptors, Muscarinic / Q000378:metabolism*
D018721:Muscarinic Agonists; D010726:Phosphodiesterase Inhibitors; D011976:Receptors, Muscarinic; D005576:Colforsin; D002217:Carbachol