Late sodium current associated cardiac electrophysiological and mechanical dysfunction

Journal article

Late sodium current (INaL) is a small sustained inward current observed during the cardiac action potential plateau phase following decay of the early peak INa. The endogenous INaL is relatively small in normal hearts but exerts functionally significant effects on cardiomyocyte repolarization with potentially pro-arrhythmic effects in hearts with reduced repolarization reserve. Enhanced INa,L occurs in long QT syndrome 3 (LQTS 3) patients, and under a number of pathological and pharmacological cardiovascular conditions, including bradycardia, myocardial ischemia, reperfusion injury, and heart failure. It may there play important roles in arrhythmogenesis and mechanical dysfunction. Experimental and clinical research suggests that INaL inhibition may prevent and treat cardiac arrhythmias and improve ventricular pump function. Selective INa,L inhibitors, exemplified by ranolazine, GS-967 and GS-458967 have little or no effect on peak sodium current and/or IKr, and carry no or minimal pro-arrhythmic risk compared to those associated with administration of classical class I or III antiarrhythmic drugs, particularly in patients with ischemic heart disease. This increased understanding of INaL may be encouraging to clinicians in use of INaL inhibitors to treat cardiac arrhythmias and mechanical dysfunction directly associated with enhanced INaL such as LQTS type 3, and myocardial ischemia. This review discusses the roles of endogenous and enhanced INaL in arrhythmogenesis and mechanical dysfunction, and the basic and clinical research of INaL inhibitors.

Authors: Yu, S; Li, G; Huang, C; Lei, M; Wu, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Verlag
• Journal: Pflügers Archiv European Journal of Physiology
• Volume: 470
• Issue: 3
• Pages: 461–469
• Publication date: 2017-11-10
• Acceptance date: 2017-10-09
• DOI: 10.1007/s00424-017-2079-7
• ISSN: 1432-2013 and 0031-6768
• Pmid: 29127493
• Language: English
• Keywords: INaL; cardiac arrhythmias; late sodium current; mechanical dysfunction antiarrhythmic drugs