The epicardium as modulator of the cardiac autonomic response during early development

Tim P. Kelder, Sjoerd N. Duim, Rebecca Vicente-Steijn, Anna M.D. Végh, Boudewijn P.T. Kruithof, Anke M. Smits, Thomas C. van Bavel, Noortje Bax, Martin J. Schalij, Adriana C. Gittenberger-de Groot, Marco C. DeRuiter, M.J.T.H Goumans, Monique R.M. Jongbloed

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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.

Original languageEnglish
Pages (from-to)251-259
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Publication statusPublished - 1 Dec 2015


  • Autonomic modulation
  • Autonomic nervous system
  • Cardiac conduction system
  • Cardiac development
  • Epicardium


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