title: Atrial natriuretic peptide regulates Ca channel in early developmental cardiomyocytes.
abstract: BACKGROUND
  Cardiomyocytes derived from murine embryonic stem (ES) cells possess various membrane currents and signaling cascades link to that of embryonic hearts. The role of atrial natriuretic peptide (ANP) in regulation of membrane potentials and Ca(2+) currents has not been investigated in developmental cardiomyocytes.
  
  
  RESULTS
  We investigated the role of ANP in regulating L-type Ca(2+) channel current (I(CaL)) in different developmental stages of cardiomyocytes derived from ES cells. ANP decreased the frequency of action potentials (APs) in early developmental stage (EDS) cardiomyocytes, embryonic bodies (EB) as well as whole embryo hearts. ANP exerted an inhibitory effect on basal I(CaL) in about 70% EDS cardiomyocytes tested but only in about 30% late developmental stage (LDS) cells. However, after stimulation of I(CaL) by isoproterenol (ISO) in LDS cells, ANP inhibited the response in about 70% cells. The depression of I(CaL) induced by ANP was not affected by either Nomega, Nitro-L-Arginine methyl ester (L-NAME), a nitric oxide synthetase (NOS) inhibitor, or KT5823, a cGMP-dependent protein kinase (PKG) selective inhibitor, in either EDS and LDS cells; whereas depression of I(CaL) by ANP was entirely abolished by erythro-9-(2-Hydroxy-3-nonyl) adenine (EHNA), a selective inhibitor of type 2 phosphodiesterase(PDE2) in most cells tested. CONCLUSION/SIGNIFICANCES: Taken together, these results indicate that ANP induced depression of action potentials and I(CaL) is due to activation of particulate guanylyl cyclase (GC), cGMP production and cGMP-activation of PDE2 mediated depression of adenosine 3', 5'-cyclic monophophate (cAMP)-cAMP-dependent protein kinase (PKA) in early cardiomyogenesis.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Miao
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Wen-Xuan
authors.initials: WX
authors.lastname: Yin
authors.forename: Qi
authors.initials: Q
authors.lastname: Yuan
authors.forename: Ying-Xiao
authors.initials: YX
authors.lastname: Chen
authors.forename: Bernd
authors.initials: B
authors.lastname: Fleischmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017931:DNA Primers; D053595:Embryonic Stem Cells / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000196:embryology / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D017931:DNA Primers; D004791:Enzyme Inhibitors; C073601:KT 5823; D005576:Colforsin; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester