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Updated: Apr 29, 2026

Confocal Imaging of Single Mitochondrial Superoxide Flashes in Intact Heart or In Vivo
Published on: November 5, 2013
Cardiomyocyte-derived mitochondrial superoxide causes myocardial electrical remodeling by downregulating potassium
Sayaka Kurokawa1, Shinichi Niwano, Hiroe Niwano
1Department of Cardiovascular Medicine, Kitasato University School of Medicine.
Background:
This study was designed to investigate the role of a primary hyperoxidative stress in myocardial electrical remodeling using heterozygous heart/muscle-specific manganese superoxide dismutase-deficient (H/M-Sod2(+/-)) mice treated with L-buthionine-sulfoximine (BSO).
Methods And Results:
Both H/M-Sod2(+/-)and wild-type (WT) mice were treated with intra-peritoneal BSO or saline for 7 days, and divided into 4 groups: H/M-Sod2(+/-)+BSO, WT+BSO, H/M-Sod2(+/-)control, and WT control. The ventricular effective refractory period (ERP) and the monophasic action potential duration (MAPD) were determined. Levels of oxidative stress, potassium channel-related molecules, and K(+)channel-interacting protein-2 (KChIP2) were also evaluated. The H/M-Sod2(+/-)+BSO group exhibited markedly prolonged MAPD20, MAPD90 and ERP in comparison with the other groups (MAPD20: 14 ± 1 vs. 11 ± 1 ms, MAPD90: 77 ± 7 vs. 58 ± 4 ms, ERP: 61 ± 6 vs. 41 ± 3 ms, H/M-Sod2(+/-)+BSO vs. WT control; P<0.05). Mitochondrial superoxide and hydrogen peroxide formation in the myocardium increased in the H/M-Sod2(+/-)+BSO group in comparison with the WT+BSO group (P<0.05). Real-time RT-PCR and Western blotting revealed that Kv4.2 expression was downregulated in both BSO-treated groups, whereas KChIP2 expression was downregulated only in the H/M-Sod2(+/-)+BSO group (P<0.05).
Conclusions:
BSO treatment caused hyperoxidative stress in the myocardium of H/M-Sod2(+/-)mice. Changes in the expression and function of potassium channels were considered to be involved in the mechanism of electrical remodeling in this model.
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