Role of apamin-sensitive small conductance calcium-activated potassium currents in long-term cardiac memory in rabbits

Background Apamin-sensitive small conductance calcium-activated K current (I KAS ) is up-regulated during ventricular pacing and masks short-term cardiac memory (CM). Objective The purpose of this study was to determine the role of I KAS in long-term CM. Methods CM was created with 3–5 weeks of ventricular pacing and defined by a flat or inverted T wave off pacing. Epicardial optical mapping was performed in both paced and normal ventricles. Action potential duration (APD 80 ) was determined during right atrial pacing. Ventricular stability was tested before and after I KAS blockade. Four paced hearts and 4 normal hearts were used for western blotting and histology. Results There were no significant differences in either echocardiographic parameters or fibrosis levels between groups. Apamin induced more APD 80 prolongation in CM than in normal ventricles (mean [95% confidence interval]: 9.6% [8.8%–10.5%] vs 3.1% [1.9%–4.3%]; P 80 in the CM model at late activation sites, indicating significant I KAS up-regulation at those sites. The CM model also had altered Ca 2+ handling, with the 50% Ca 2+ transient duration and amplitude increased at distal sites compared to a proximal site (near the pacing site). After apamin, the CM model had increased ventricular fibrillation (VF) inducibility (paced vs control: 33/40 (82.5%) vs 7/20 (35%); P P Conclusion Chronic ventricular pacing increases Ca 2+ transients at late activation sites, which activates I KAS to maintain repolarization reserve. I KAS blockade increases VF vulnerability in chronically paced rabbit ventricles.