title: The control of cardiac ventricular excitability by autonomic pathways.
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.
authors.affiliation: The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M6BQ, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Finlay
authors.affiliation: The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M6BQ, UK.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harmer
authors.affiliation: The Heart Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M6BQ, UK. Electronic address: a.tinker@qmul.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tinker
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000378:metabolism*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology*; D009154:Mutation; D015398:Signal Transduction; D013550:Swimming / Q000502:physiology
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: Autonomic nervous system; Cardiac arrhythmia; Cardiac ventricle; Conduction velocity; Excitability; Ion channels