Transcriptional regulation of the cardiac conduction system

Nat Rev Cardiol. 2018 Oct;15(10):617-630. doi: 10.1038/s41569-018-0031-y.


The rate and rhythm of heart muscle contractions are coordinated by the cardiac conduction system (CCS), a generic term for a collection of different specialized muscular tissues within the heart. The CCS components initiate the electrical impulse at the sinoatrial node, propagate it from atria to ventricles via the atrioventricular node and bundle branches, and distribute it to the ventricular muscle mass via the Purkinje fibre network. The CCS thereby controls the rate and rhythm of alternating contractions of the atria and ventricles. CCS function is well conserved across vertebrates from fish to mammals, although particular specialized aspects of CCS function are found only in endotherms (mammals and birds). The development and homeostasis of the CCS involves transcriptional and regulatory networks that act in an embryonic-stage-dependent, tissue-dependent, and dose-dependent manner. This Review describes emerging data from animal studies, stem cell models, and genome-wide association studies that have provided novel insights into the transcriptional networks underlying CCS formation and function. How these insights can be applied to develop disease models and therapies is also discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials
  • Animals
  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / therapy
  • Biological Clocks* / genetics
  • Cell Transplantation / methods
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental
  • Genetic Therapy / methods
  • Heart Conduction System / metabolism*
  • Heart Conduction System / physiopathology
  • Heart Rate* / drug effects
  • Humans
  • Organogenesis
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Transcription Factors