生物活性

• 靶点

  Potassium Channel Kv1.5 (I508F) IC50:0.61±0.03μM

  Potassium Channel Kv1.5 (T479A) IC50:1.63±0.09μM

  Potassium Channel Kv1.5 IC50:13.35±0.93μM

• 描述Kv1.5 underlies the ultrarapid delayed rectifier outward K⁺ currents that are observed naturally in atrium of heart, whereas they appear to be absent from ventricle. Kv1.5 play an important role in determining the length of cardiac action potentials and, therefore, have been the targets of antiarrhythmic drugs . Vernakalant, a mixed voltage- and frequency-dependent Na⁺ and atria-preferred K⁺ channel blocker, is used to convert atrial fibrillation rapidly and safely in patients. Block by vernakalant of Kv1.5 wild type and mutants was assessed in transiently transfected human embryonic kidney 293 cells. The IC₅₀ values were 13.35±0.93 μM, 0.61±0.03 μM, and 1.63±0.09 μM for Kv1.5 channel^wt, Kv1.5 channel^I508F, Kv1.5 channel^T479A, respectively. In the presence of 10 μM vernakalant, rapid block was apparent after channel opening, and a steady-state currentlevel was rapidly reached. Upon repolarization, the tail current amplitude was initially less than in control, but decayed more slowly and crossed over the control tracing as it declined to thebaseline current level suggesting that vernakalant delayed closing of Kv1.5 .
• 作用机制Ile502 in the S6 domain is a key residue in the block of Kv1.5 by vernakalant .