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 2132±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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 558-570 |
| Number of pages | 13 |
| Journal | Circulation Research |
| Volume | 86 |
| Issue number | 5 |
| State | Published - Mar 17 2000 |
| Externally published | Yes |
Fingerprint
Keywords
- Action potential
- Ca current
- Cardiac failure
- Cardiac hypertrophy
- Guinea pig
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Changes in Ca2+ cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure. / Ahmmed, Gias U.; Dong, Pei Hong; Song, Guoji; Ball, Nancy A.; Xu, Yanfang; Walsh, Richard A.; Chiamvimonvat, Nipavan.
In: Circulation Research, Vol. 86, No. 5, 17.03.2000, p. 558-570.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Changes in Ca2+ cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure
AU - Ahmmed, Gias U.
AU - Dong, Pei Hong
AU - Song, Guoji
AU - Ball, Nancy A.
AU - Xu, Yanfang
AU - Walsh, Richard A.
AU - Chiamvimonvat, Nipavan
PY - 2000/3/17
Y1 - 2000/3/17
N2 - 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 2132±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.
AB - 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 2132±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.
KW - Action potential
KW - Ca current
KW - Cardiac failure
KW - Cardiac hypertrophy
KW - Guinea pig
UR - http://www.scopus.com/inward/record.url?scp=0343674495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0343674495&partnerID=8YFLogxK
M3 - Article
C2 - 10720418
AN - SCOPUS:0343674495
VL - 86
SP - 558
EP - 570
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 5
ER -