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

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 (퐼Ca-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 patchclampwasusedtorecordactionpotential (AP)and 퐼Ca-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 퐼Ca-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak 퐼Ca-L, accelerated 퐼Ca-L inactivation, and positive frequency-dependent 퐼Ca-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 퐼Ca-L remodeling by downregulating CaMKII. 1.