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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 (IKAS) 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 IKAS 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 (APD80) was determined during right atrial pacing. Ventricular stability was tested before and after IKAS 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 APD80 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 <.001). Apamin significantly lengthened APD80 in the CM model at late activation sites, indicating significant IKAS up-regulation at those sites. The CM model also had altered Ca2+ handling, with the 50% Ca2+ 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 <.001) and longer VF durations (124 vs 26 seconds; P <.001). CONCLUSION:Chronic ventricular pacing increases Ca2+ transients at late activation sites, which activates IKAS to maintain repolarization reserve. IKAS blockade increases VF vulnerability in chronically paced rabbit ventricles.

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