title: Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages.
abstract: OBJECTIVE
  To investigate the muscarinic regulation of L-type calcium current (I(Ca-L)) during development.
  
  
  METHODS
  The whole cell patch-clamp technique was used to record II(Ca-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 I(Ca-L) density did not change in different developmental stages (P>0.05). There was no difference in the sensitivity of I(Ca-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 I(Ca-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.
  
  
  CONCLUSIONS
  The inhibitory action of CCh on I(Ca-L) current was mediated in different pathways: in EDS, the inhibitory action of M-receptor on I(Ca-L) channel mainly depended on the stimulation of PDE. However, in LDS, the regulation by M-receptor on I(Ca-L) channel mainly depended on the inactivation of AC.
authors.affiliation: Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hua-min
authors.initials: HM
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: Tang
authors.forename: Chang-jin
authors.initials: CJ
authors.lastname: Liu
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Luo
authors.forename: Yuan-long
authors.initials: YL
authors.lastname: Song
authors.forename: Xin-wu
authors.initials: XW
authors.lastname: Hu
authors.forename: Jiao-ya
authors.initials: JY
authors.lastname: Xi
authors.forename: Lin-lin
authors.initials: LL
authors.lastname: Gao
authors.forename: Bin
authors.initials: B
authors.lastname: Nie
authors.forename: Su-yun
authors.initials: SY
authors.lastname: Li
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Lai
authors.forename: Juergen
authors.initials: J
authors.lastname: Hescheler
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000196:embryology*; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology
chemical_list: D020746:Calcium Channels, L-Type; D018721:Muscarinic Agonists; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002217:Carbachol; D015056:1-Methyl-3-isobutylxanthine