Increased phosphorylation of Ca2+ handling proteins as a proarrhythmic mechanism in myocarditis

Hyelim Park, Hyewon Park, Dajeong Lee, Sujung Oh, Jisoo Lim, Hye Jin Hwang, Sungha Park, Hui Nam Pak, Moon Hyoung Lee, Boyoung Joung, Hyelim Park

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24 Citations (Scopus)


Methods and Results: Myocarditis was induced by injection of 2 mg porcine cardiac myosin into the footpads of adult Lewis rats on days 1 and 8 (Myo, n=15) and the results compared with Control rats (Control, n=15). In an additional 15 rats, 6 mg/kg prednisolone was injected into the gluteus muscle before the injection of porcine cardiac myosin on days 1 and 8 (MyoS, n=15). Hearts with myocarditis had longer action potential duration (APD), slower conduction velocity (CV; P<0.01 vs. Control), higher CV heterogeneity, greater fibrosis, higher levels of immunoblotting of high-mobility group protein B1, interleukin 6 and tumor necrosis factor-α proteins. Steroid treatment partially reversed the translations for myocarditis, CV heterogeneity, reduced APD at 90% recovery to baseline, increased CV (P<0.01), and reversed fibrosis (P<0.05). Programmed stimulation triggered sustained ventricular tachycardia in Myo rats (n=4/5), but not in controls (n=0/5) or Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor (KN93) treated Myo rats (n=0/5, P=0.01). CaMKII autophosphorylation at Thr287 (201%), and RyR2 phosphorylation at Ser2808 (protein kinase A/CaMKII site, 126%) and Ser2814 (CaMKII site, 21%) were increased in rats with myocarditis and reversed by steroid.

Conclusions: The myocarditis group had an increased incidence of arrhythmia caused by increased phosphorylation of Ca2+ handling proteins. These changes were partially reversed by an antiinflammatory treatment and CaMKII inhibition.

Background: Because fatal arrhythmia is an important cause of death in patients with myocarditis, we investigated the proarrhythmic mechanisms of experimental autoimmune myocarditis.

Original languageEnglish
Pages (from-to)2292-2301
Number of pages10
JournalCirculation Journal
Issue number9
Publication statusPublished - 2014 Sept 1

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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