Vernakalant is a new antiarrhythmic drug approved for rapid conversion of recent-onset atrial fibrillation. Its selectivity for atrial tissue over ventricular tissue is explained by:

• A Selective inhibition of IKs (slow delayed rectifier K+ current) in the atrial conduction system
• B Preferential block of IKur (ultra-rapid delayed rectifier K+ current) and INa channels expressed predominantly in atria ✓
• C Blockade of ICaL (L-type Ca2+ channels) which are denser in atrial than ventricular cells
• D High affinity for Nav1.5 isoforms uniquely expressed in atrial sinoatrial node cells

Explanation

Vernakalant blocks multiple ion channels but its atrial selectivity stems primarily from blockade of IKur (Kv1.5, ultra-rapid delayed rectifier potassium current) and Ito (transient outward potassium current), which are expressed predominantly in human atrial myocytes and are largely absent from ventricles. It also causes use-dependent and frequency-dependent blockade of atrial INa. These atrial-specific channels maintain the short atrial action potential and contribute to AF maintenance. This atrial selectivity translates to minimal pro-arrhythmic ventricular risk. IKs and ICaL are present in both chambers; Nav1.5 is a pan-cardiac isoform not restricted to atria.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.