title: The epicardium as modulator of the cardiac autonomic response during early development.
abstract: The cardiac autonomic nervous system (cANS) modulates heart rate, contraction force and conduction velocity. The embryonic chicken heart already responds to epinephrine prior to establishment of the cANS. The aim of this study was to define the regions of the heart that might participate in modulating the early autonomic response to epinephrine. Immunofluorescence analysis reveals expression of neural markers tubulin beta-3 chain and neural cell adhesion molecule in the epicardium during early development. In addition, expression of the β2 adrenergic receptor, the receptor for epinephrine, was found in the epicardium. Ex-ovo micro-electrode recordings in hearts with inhibition of epicardial outgrowth showed a significantly reduced response of the heart rate to epinephrine compared to control hearts. This study suggests a role for the epicardium as autonomic modulator during early cardiac development.
authors.affiliation: Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tim P
authors.initials: TP
authors.lastname: Kelder
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sjoerd N
authors.initials: SN
authors.lastname: Duim
authors.affiliation: Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; ICIN Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Vicente-Steijn
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anna M D
authors.initials: AM
authors.lastname: Végh
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Boudewijn P T
authors.initials: BP
authors.lastname: Kruithof
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anke M
authors.initials: AM
authors.lastname: Smits
authors.affiliation: Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: van Bavel
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
authors.forename: Noortje A M
authors.initials: NA
authors.lastname: Bax
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.affiliation: Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.affiliation: Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marco C
authors.initials: MC
authors.lastname: DeRuiter
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.j.t.h.goumans@lumc.nl.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.r.m.jongbloed@lumc.nl.
authors.forename: Monique R M
authors.initials: MR
authors.lastname: Jongbloed
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000196:embryology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002642:Chick Embryo; D047108:Embryonic Development; D004837:Epinephrine / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010496:Pericardium / Q000196:embryology* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D025721:WT1 Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011943:Receptors, Adrenergic, beta; D014404:Tubulin; D025721:WT1 Proteins; D004837:Epinephrine
keywords: Autonomic modulation; Autonomic nervous system; Cardiac conduction system; Cardiac development; Epicardium