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Laboratory Research
Age-related increase of early afterdepolarization in calsequestrin-2 knock-in mouse cardiomycyte
Yun-Feng Lan,Yi Wen,Zhou Fang,Jin-Lao Gao,Yan Liu,Men Lin,Hong-Juan Wang,Yi-Cheng Fu,Prori S.G,Carlo.Napolitano C,Yang Li.J Geriatr Cardiol 2010,7(4):171~175
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Authors:Yun-Feng Lan1;Yi Wen1;Zhou Fang1;Jin-Lao Gao1;Yan Liu1;Men Lin1;Hong-Juan Wang1;Yi-Cheng Fu1;Prori S.G2;Carlo.Napolitano C2;Yang Li3

Author Affiliation:1.Institute of Geriatric Cardiology of Chinese PLA General Hospital, Beijing 100853, China;2.Molecular Cardiology, IRCCS Fondazione S. Maugeri, Pavia, Italy; the Department of Cardiology, University of Pavia, Pavia , Italy;3.Institute of Geriatric Cardiology of Chinese PLA General Hospital, Beijing 100853, China


Abstract: Objective To characterize early afterdepolarizations (EADs) caused triggered activity (TA) among calsequestrin-2 (CASQ2) knock-in (CASQ2 KI) mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3-month (mo, young), 9-mo (adult-1) and 12-mo (adult-2) in wild-type (WT) and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential (APD50) showed prolongation in both 9-mo and 12-mo ones (9.2±0.9 ms of 9-mo and 10.3±1.2 ms of 12-mo vs. 5.6±0.3 ms of 3-mo), while the 90 % repolarization of action potential (APD90) was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current (Ito) densities but increased L-type calcium current (ICa-L) densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age. It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice (J Geriatr Cardiol 2010; 7:171-175).


Calsequestrin; early afterdepolarization; triggered activity; gene mutation; transgenic mice
          Published Online:December 28, 2010
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