Ultra Rapid delayed rectifier potassium current blockers in AF

Ultra Rapid delayed rectifier potassium current blockers in AF

Ultra Rapid delayed rectifier potassium current blockers in AF: Suppression of atrial fibrillation with drugs has always been a difficult issue. Most agents which suppress atrial fibrillation have certain problems like pro-arrhythmia or extra cardiac side effects. A novel strategy which has been proposed is the development of agents which act preferentially on the atria rather than on the ventricles. The ultra rapid delayed rectifier potassium current (I_Kur) is expressed in the atria, but not in the ventricles. Inhibition of I_Kur has been considered as an atrial selective antiarrhythmic treatment.

Vernakalant inhibits I_Kur and I_KAch at low concentration. These are atrial specific potassium channels. At higher concentrations, it can blockI_to and I_Na also [1]. Vernakalant is a rapidly acting drug useful in the treatment of recent onset atrial fibrillation.

Atrial selective sodium channel blockade [2] with drugs like ranolazine is another approach which has been evaluated.

Kv 1.5 channels are responsible for  the I_Kur and Kv 1.5 channels are encoded by the gene KCNA5. Some concern has been raised because I_Kur block may abbreviate atrial repolarization and loss of function mutations in KCNA5 has been associated with familial atrial fibrillation [3].

Reference

1. Lei Chen, Kevin J Sampson 1, Robert S Kass. Cardiac Delayed Rectifier Potassium Channels in Health and Disease. Card Electrophysiol Clin. 2016 Jun;8(2):307-22.
2. Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C. Atrial-selective sodium channel block as a strategy for suppression of atrial fibrillation. Ann N Y Acad Sci. 2008 Mar;1123:105-12.
3. Burashnikov A, Antzelevitch C. Can inhibition of IKur promote atrial fibrillation? Heart Rhythm. 2008 Sep;5(9):1304-9.