Changes in Ca2+ cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure

Ventricular arrhythmias are common in both cardiac hypertrophy and failure; cardiac failure in particular is associated with a significant increase in the risk of sudden cardiac death. We studied the electrophysiologic change s in a guinea pig model with aortic banding resulting in cardiac hypertroph y at 4 weeks and progressing to cardiac failure at 8 weeks using whole-cell patch-clamp and biochemical techniques. Action potential durations (APDs) were significantly prolonged in banded animals at 4 and 8 weeks compared wi th age-matched sham-operated animals. APDs at 50% and 90% repolarization (A PD(50) and APD(90) in ms) were the following: 4 week, banded, 208+/-51 and 248+/-49 (n = 15); 4 week, sham, 189+/-68 and 213+/-69 (n = 16); 8 week, ba nded, 197+/-40 and 226+/-40 (n = 21); and 8 week, sham, 156+/-42 and 189+/- 45 (n = 22), respectively; P<0.05 comparing banded versus sham-operated ani mals. We observed no significant differences in the K+ currents between the 2 groups of animals at 4 and 8 weeks. However, banded animals exhibited a significant increase in Na+ and Na+-Ca2+ exchange current densities compare d with controls. Furthermore, we have found a significant attenuation in th e Ca2+-dependent inactivation of the L-type Ca2+ current in the banded comp ared with sham-operated animals, likely as a result of the significant down regulation of the sarcoplasmic reticulum Ca2+ ATPase, which has been docume nted previously in the heart failure animals. Our data provide an alternate mechanism for APD prolongation in cardiac hypertrophy and failure and supp ort the notion that there is close interaction between Ca2+ handling and ac tion potential profile.