Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages  

作　　者：Hua-minLIANG MingTANG Chang-jinLIU Hong-yanLUO Yuan-longSONG Xin-wuHU Jiao-yaXI Lin-linGAO BinNIE Su-yunLI Ling-lingLAI JuergenHESCHELER 

机构地区：[1]DepartmentofPhysiology,TongjiMedicalCollegeofHuazhongUniversityofScienceandTechnology,Wuhan430030,China [2]InstituteofNeurophysiology,UniversityofCologne,D-50931Cologne,Germany

出　　处：《Acta Pharmacologica Sinica》2004年第11期1450-1457,共8页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(No30070279).

摘　　要：AIM: To investigate the muscarinic regulation of L-type calcium current (ICa_L) during development. METHODS: The whole cell patch-clamp technique was used to record ICa_L in mice embryonic cardiomyocytes at different stages (the early developmental stage, EDS; the intermediate developmental stage, IDS; and the late developmental stage, LDS). Carbachol (CCh) was used to stimulate M-receptor in the embryonic cardiomyocytes of mice. RESULTS: The expression of 7Ca-L density did not change in different developmental stages (P>0.05). There was no difference in the sensitivity of ICa_L to CCh during development (P>0.05). This inhibitory action of CCh was mediated by inhibition of cyclic AMP since 8-bromo-cAMP completely reversed the muscarinic inhibitory action. IBMX, a non-selective inhibitor of phosphodiesterase (PDE), reversed the inhibitory action of M-receptor on 7Ca-L current by 71.2 %±9.2 % (n=8) and 11.3 %±2.5 % (n=9) in EDS and LDS respectively. However forskolin, an agonist of adenylyl cyclase (AC), reversed the action of CCh by 14.5 %±3.5 % (n=5) and 82.7 %±10.4 % (n=7) in EDS and LDS respectively. CONCLUSION: The inhibitory action of CCh on ICa-L current was mediated in different pathways: in EDS, the inhibitory action of M-receptor on ICa-L channel mainly depended on the stimulation of PDE. However, in LDS, the regulation by M-receptor on ICa-L channel mainly depended on the inactivation of AC.AIM: To investigate the muscarinic regulation of L-type calcium current (ICa_L) during development. METHODS: The whole cell patch-clamp technique was used to record ICa_L in mice embryonic cardiomyocytes at different stages (the early developmental stage, EDS; the intermediate developmental stage, IDS; and the late developmental stage, LDS). Carbachol (CCh) was used to stimulate M-receptor in the embryonic cardiomyocytes of mice. RESULTS: The expression of 7Ca-L density did not change in different developmental stages (P>0.05). There was no difference in the sensitivity of ICa_L to CCh during development (P>0.05). This inhibitory action of CCh was mediated by inhibition of cyclic AMP since 8-bromo-cAMP completely reversed the muscarinic inhibitory action. IBMX, a non-selective inhibitor of phosphodiesterase (PDE), reversed the inhibitory action of M-receptor on 7Ca-L current by 71.2 %±9.2 % (n=8) and 11.3 %±2.5 % (n=9) in EDS and LDS respectively. However forskolin, an agonist of adenylyl cyclase (AC), reversed the action of CCh by 14.5 %±3.5 % (n=5) and 82.7 %±10.4 % (n=7) in EDS and LDS respectively. CONCLUSION: The inhibitory action of CCh on ICa-L current was mediated in different pathways: in EDS, the inhibitory action of M-receptor on ICa-L channel mainly depended on the stimulation of PDE. However, in LDS, the regulation by M-receptor on ICa-L channel mainly depended on the inactivation of AC.

关 键 词：8-bromo cyclic adenosine monophosphate calcium channels cell differentiation embryo and fetal development FORSKOLIN HEART MICE patch-clamp techniques muscarinic receptors 

分 类 号：R714.5[医药卫生—妇产科学]