Dynamic changes of electrical remodeling in midmyocardium of rabbit left ventricle during the early stage of chronic pressure-overload / 生理学报

ABSTRACT

In the previous study, we had found that the action potential duration (APD) of midmyocardial (M) cells was gradually prolonged and M cells were easier to produce early after-depolarization (EAD) in the rabbit left ventricle during the early stage of chronic pressure-overload. The present study was performed to investigate the dynamic changes and significance of ionic current remodeling in M cells of rabbit left ventricle during the early stage of chronic pressure-overload. Sixty-four New Zealand rabbits were randomly divided into constriction groups and sham groups. The rabbit models with chronic pressure-overload were prepared by partial constriction of suprarenal abdominal aorta at the site proximal 5-10 mm away from the left renal artery. At 2 and 8 weeks after operation, the single cardiomyocytes were isolated by enzymatic digestion method. The midmyocardium from the anterolateral free wall of left ventricle was obtained by removing the epicardial and endocardial surfaces. Whole-cell patch-clamp technique was used to record the slowly activating delayed rectifier potassium current (I(Ks)), transient outward potassium current (I(to)), L-type calcium current (I(Ca-L)) of M cells. At 2 weeks after the constriction operation, compared with the sham group, I(Ks) tail current (I(Ks,tail)) and I(to) densities of M cells from constriction group significantly decreased by 33.3% and 51.5%, respectively. There was no significant difference in I(Ca-L) density between the two groups. At 8 weeks after operation, compared with the sham group, I(Ks,tail) and I(to) densities of M cells from constriction group significantly decreased by 37.0% and 49.2%, respectively. There was still no significant difference in I(Ca-L) density between the two groups. These results suggest that during the early phase of chronic pressure-overload, the electrical remodeling of M cells in rabbit left ventricle has developed, representing as the down regulations of I(Ks) and I(to) that can lead to the prolongation of APD, which might be a risk factor for the occurrence of malignant arrhythmia.