Abstract 21122: Small Conductance Calcium Activated Potassium Channel and Recurrent Ventricular Fibrillation in Failing Rabbit Ventricles
Background: Recurrent spontaneous ventricular fibrillation (SVF), or electrical storm, is associated with increased mortality and morbidity. Action potential duration (APD) shortening and late phase 3 early afterdepolarization after fibrillation-defibrillation episodes are associated with electrical storm in failing rabbit ventricles. However, the mechanisms of acute APD shortening remain unclear.
Hypothesis: We hypothesize apamin-sensitive small conductance calcium activated potassium channels (SK) are responsible for APD shortening after fibrillation-defibrillation episodes in failing ventricles.
Methods and Results: Simultaneous optical mapping of intracellular calcium and membrane potential was performed in Langendorff-perfused failing hearts (N=9, among them 2 have SVF), sham-operated hearts (N=2), and normal hearts (N=7). The magnitude of APD shortening increased with increasing pacing cycle rate and duration. Apamin (1 μmol/L), a specific SK channel inhibitor, reduced the magnitude of APD shortening only in failing ventricles. The differences of postshock APD before and after apamin is 30.7 ms (range 14.9 ms to 64.4 ms, p<0.001) for SVF group, 15.7 ms (range 9.4 ms to 21.9 ms, p<0.001) for no-SVF group, and 5.8ms (range −2.2 ms to 13.8 ms; p=NS) for normal ventricles, respectively. Apamin eliminated recurrent SVF episodes. Whole cell patch clamp studies confirmed that apamin-sensitive potassium currents (IKAS) was significantly larger in failing ventricular cells than in the normal cells. Glibenclamide, an ATP-sensitive potassium channel inhibitor, did not prevent post-pacing or postshock APD shortening in 3 failing ventricles.
Conclusions: In failing ventricles, increased IKAS underlies the mechanisms of APD shortening and electrical storm, and IKAS inhibition may be a novel approach to antiarrhythmic therapy.
- © 2010 by American Heart Association, Inc.