Abstract 16846: Calcium-Activated Potassium Current Modulates Ventricular (but Not Atrial) Repolarization in Chronic Heart Failure
In chronic canine HF (and in human HF) atrial repolarization is shortened while ventricular repolarization is prolonged. We hypothesized that chamber-specific differences in calcium-activated potassium current (IKCa) contribute to HF-induced repolarization changes.
METHODS: A chronic (4 month) canine model of tachypacing-induced HF was used. Action potential durations (APDs) in left atrial (LA) and ventricular (LV) myocytes were recorded before and after the application of 100 nM apamin, an IKCa blocker. Adjacent tissues were collected to measure sK2 and sK3, proteins which underlie cardiac IKCa.
RESULTS: HF resulted in an ∼19% shortening of the atrial APD (p<0.05, 1 Hz) and an ∼25% prolongation of ventricular APD compared to controls (p<0.05, 1 Hz). In HF LA, sK2 was increased ∼3-fold (p<0.05) while sK3 was unchanged. In the LV, sK2 was unchanged (p=0.11) while sK3 was increased ∼4-fold (p<0.05). Apamin (0.5-100 nM) did not alter APD or increase beat to beat variability (B2BV) of the APD in normal LV cells. In contrast, apamin significantly increased APD50 and APD90 in HF LV cells in a reverse-rate dependent manner, and also increased B2BV (p<0.05), consistent with proarrhythmic potential. However, in the HF LA cells apamin had no significant effect on APD50 or 90, and reduced B2BV.
CONCLUSIONS: In HF, IKCa modulates LV repolarization. However, in the LA where HF reduces the APD through increased repolarizing current, IKCa has little effect on LA repolarization. The lack of effect of IKCa block in the HF LA is explained by accelerated repolarization which significantly reduces Ica - an effect which reduces IKCa. In the HF LV, where repolarization reserve is reduced, block of IKCa may be proarrhythmic.
- © 2012 by American Heart Association, Inc.