Age-related increase of early afterdepolarization in calsequestrin-2 knock-in mouse cardiomycyte

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.