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Astragalus Granule Prevents Ca 2 + Current Remodeling in Heart Failure by the Downregulation of CaMKII

Sinai Li, Yibing Nong, Qun Gao, Jing Liu, Yan Li, Xiaoyun Cui, Jie Wan, Jinjin Lu, Mingjie Sun, Qian Wu, Xiaolu Shi, Haifeng Cui, Weihong Liu, Mingxue Zhou, Lina Li, Qian Lin
Evidence-Based Complementary and Alternative Medicine2017
Background. Astragalus was broadly used for treating heart failure (HF) and arrhythmias in East Asia for thousands of years. Astragalus granule (AG), extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca2+ current (ICa-L) inHF mice by the downregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). Methods. HF mice were induced by thoracic aortic constriction (TAC). Aſter 4 weeks of AG treatment, cardiac function and QT interval were evaluated. Single cardiac ventricular myocyte wasthenisolatedand whole-cell patch clamp was used to record action potential (AP)and ICa-L.Theexpressions of L-type calcium channel alpha 1C subunit (Cav1.2), CaMKII, and phosphorylated protein kinase A (p-PKA) were examined by western blot. Results. The failing heart manifested distinct electrical remodeling including prolonged repolarization time and altered ICa-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak ICa-L, accelerated ICa-L inactivation, and positive frequency-dependent ICa-L facilitation. In addition,AGtreatment suppressed the overexpression of CaMKII, but not p-PKA, in the failing heart. Conclusion. AG treatment protected the failing heart against electrical remodeling and ICa-L remodeling by downregulating CaMKII.
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