© 2000 American Heart Association, Inc.
Integrative Physiology |
Changes in Ca2+ Cycling Proteins Underlie Cardiac Action Potential Prolongation in a Pressure-Overloaded Guinea Pig Model With Cardiac Hypertrophy and Failure
From the Division of Cardiology, Department of Medicine (G.U.A., P.H.D., N.A.B., Y.X., N.C.), University of Cincinnati, Ohio; University College London (G.S.), United Kingdom; and Department of Medicine (R.A.W.), Case Western Reserve University, Cleveland, Ohio.
Correspondence to Nipavan Chiamvimonvat, Division of Cardiology, Department of Medicine, University of Cincinnati, MSB 3354, 231 Bethesda Ave, Cincinnati, OH 45267-0542.
Abstract—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 changes in a guinea pig model with aortic banding resulting in cardiac hypertrophy 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 with age-matched sham-operated animals. APDs at 50% and 90% repolarization (APD50 and APD90 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, banded, 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 animals. 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 compared with controls. Furthermore, we have found a significant attenuation in the Ca2+-dependent inactivation of the L-type Ca2+ current in the banded compared with sham-operated animals, likely as a result of the significant downregulation of the sarcoplasmic reticulum Ca2+ ATPase, which has been documented previously in the heart failure animals. Our data provide an alternate mechanism for APD prolongation in cardiac hypertrophy and failure and support the notion that there is close interaction between Ca2+ handling and action potential profile.
Key Words: cardiac hypertrophy • cardiac failure • action potential • guinea pig • Ca2+ current
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