Issue Archive

Transmural L--type calcium current in a pressure--overloaded mouse model with heart failure

Shi Chenxia, Wang Yuhong, Dong Fang, Zhang Yongjian, Xu Yanfang

Department of Pharmacology, School of Basic Medicine, Hebei Medical University.Shijiazhuang 050017,Hebei

Abstract

Transmural electrical heterogeneity plays an important role in the normal dispersion of repolarizaion and propagation of excitation in the heart. The amplification of transmural electrical heterogeneity contributes to the genesis of arrhythmias in cardiac hypertrophy and failure. We established a mouse model with cardiac failure by aortic handing and investigated the possible contribution of L-type calcium current （I_(Ca-L)） to transmural electrical heterogeneity in both normal and failing hearts. Single myocytes were enzymatically isolated from suhendocardial and suhepicardial myocardium of the free left ventricle wall. The recordings of action potential and I_(Ca-L) were performed using the conventional whole-cell patch-clamp technique. The results showed that： （1） The action potential duration at 90% repolarization （APD_(90)） of the suhendocardial myocytes in normal control mice was （38.2±6.44） ms, which was significantly longer than that of the suhepicardial myocytes [（15.67±5.31） ms]. The ratio of APD_(90) for suhendocardial/suhepicardial myocytes was about 2.5:1. The peak I_(Ca-L) density in subendocardial myocytes was （-2.7±0.49） pA/pF, which was not different from that in suhepicardial myocytes [（-2.54±0.53） pA/pF]. （2） In failing hearts, both action potential duration at 50% repolarization （APD_(90)） and APD_(90) were remarkably prolonged either in suhendocardial or subepicardial myocytes compared to that in sham hearts. The subendocardial myocytes had much longer APD. The ratio of APD00 for subendocardial/subepicardial myocytes changed to about 4.2:1. （3） I_(Ca-L) density in subendocardial myocytes was significantly decreased in failing hearts compared with that in sham hearts. At four test potentials from +10 mV to +40 mV, the density of I_(Ca-L) from subendocardial myocytes in failing hearts was decreased by 20.2%, 21.4%, 21.6% and 25.7%, respectively （P〈0.01）. However, no significant difference was observed in I_(Ca-L) density from subepicardial myocytes in failing hearts. There was no significant difference in the kinetic properties of I_(Ca-L) in subendocardial and subepicardial myocytes between the band and sham groups. We conclude that I_(Ca-L) may not contribute to the physiological transmural electrical heterogeneity in mouse hearts. The electrical heterogeneity is exaggerated and the density of I_(Ca-L) is decreased in the subendocardial myocytes, but not in the subepicardial myocytes in failing hearts. The results obtained suggest that the decreased density of I_(Ca-L) in subendocardial myocytes is possibly an adaptive response to the prolongation of action potential due to delayed depolarization and may reduce the transmural dispersion of repolarization in heart failure.

Key words: Action potential;L-type calcium current;heart failure;transmural electrical heterogeneity;Mouse

Received: 　　Accepted:

Corresponding author: 　　E-mail:

Citing This Article：

Shi Chenxia, Wang Yuhong, Dong Fang, Zhang Yongjian, Xu Yanfang. Transmural L--type calcium current in a pressure--overloaded mouse model with heart failure. Acta Physiol Sin 2007; 59 (1): 19-26 (in Chinese with English abstract).