This report was presented at a Cardiac & Respiratory Physiology Themed Meeting of The Physiological Society, Manchester, UK, 4–6 September 2012.
Funny channel gene mutations associated with arrhythmias
Article first published online: 17 APR 2013
© 2013 The Author. The Journal of Physiology © 2013 The Physiological Society
The Journal of Physiology
Special Issue: Special cardiovascular issue
Volume 591, Issue 17, pages 4117–4124, September 2013
How to Cite
DiFrancesco, D. (2013), Funny channel gene mutations associated with arrhythmias. The Journal of Physiology, 591: 4117–4124. doi: 10.1113/jphysiol.2013.253765
- Issue published online: 30 AUG 2013
- Article first published online: 17 APR 2013
- Accepted manuscript online: 22 MAR 2013 12:28PM EST
- (Received 21 February 2013; accepted after revision 17 March 2013; first published online 18 March 2013)
Abstract Many diverse data support a role of the funny current (If) in pacemaking and heart rate control. Among them, clinically relevant applications have special impact, since they translate the concept of funny channel-based pacemaking into practical developments of potential therapeutic value. For example, the If role in pacemaking is the basis for a pharmacological approach to heart rate control. Ivabradine, a specific f-channel blocker acting as a ‘pure heart rate reducing’ agent, is used today as a therapeutic tool in chronic stable angina and heart failure. Also, the pacemaking capability of funny channels has been the main rationale behind the development of ‘biological’ pacemakers, whose aim is to eventually replace the electronic pacemakers implanted today. Finally, the role of If in pacemaking implies that dysfunctional funny channels can contribute to rhythm disorders. This consideration has led to the search for inheritable forms of cardiac arrhythmias potentially linked to functional changes of HCN4 channels, the molecular correlates of funny channels. This review addresses recent reports where investigation of families with arrhythmias has allowed the identification of specific HCN4 channel mutations associated with different types of rhythm disorders, specifically with sinus bradycardia. The perspective of future research in this field is also addressed.