The control of cardiac ventricular excitability by autonomic pathways

Malcolm Finlay, Stephen C Harmer, Andrew Tinker

Research output: Contribution to journalReview article (Academic Journal)peer-review

275 Downloads (Pure)

Abstract

Central to the genesis of ventricular cardiac arrhythmia are variations in determinants of excitability. These involve individual ionic channels and transporters in cardiac myocytes but also tissue factors such as variable conduction of the excitation wave, fibrosis and source-sink mismatch. It is also known that in certain diseases and particularly the channelopathies critical events occur with specific stressors. For example, in hereditary long QT syndrome due to mutations in KCNQ1 arrhythmic episodes are provoked by exercise and in particular swimming. Thus not only is the static substrate important but also how this is modified by dynamic signalling events associated with common physiological responses. In this review, we examine the regulation of ventricular excitability by signalling pathways from a cellular and tissue perspective in an effort to identify key processes, effectors and potential therapeutic approaches. We specifically focus on the autonomic nervous system and related signalling pathways.

Original languageEnglish
Pages (from-to)97-111
Number of pages15
JournalPharmacology and Therapeutics
Volume174
Early online date14 Feb 2017
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • Animals
  • Arrhythmias, Cardiac/genetics
  • Autonomic Nervous System/metabolism
  • Humans
  • KCNQ1 Potassium Channel/genetics
  • Long QT Syndrome/genetics
  • Mutation
  • Signal Transduction
  • Swimming/physiology

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