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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
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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,but its effects on HF-associated electrical remodeling have not been addressed.We hypothesized that administration of AG could prevent the remodeling of L-type Ca2+ current (ICa-L) in mice with HF by the downregulation of Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ).Methods: HF was induced by thoracic aortic constriction (TAC) in a mouse model.After TAC,animals were assigned into AG group or control group.Four weeks after AG treatment,cardiac function and QT interval were evaluated by echocardiogram and electrocardiogram,respectively.Single cardiac ventricular myocyte was then isolated from the heart.Action potential (AP) and ICa-L were recorded using the whole-cell patch clamp technique.The expression of L-type calcium channel alpha 1C subunit (Cavl.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.Animals in AG group showed shortened QT interval.Myocytes from the mice in AG group showed shortened AP duration,decreased peak ICa-L,accelerated ICa-L inactivation and positive frequency-dependent ICa-L facilitation.These results indicated AG treatment attenuated the pathological electrical remodeling in failing heart.Accompanied with that,western blots data suggested AG treatment suppressed the overexpression of CaMKⅡ,but not p-PKA,in the failing heart.Conclusion: These findings revealed that AG treatment protected the failing heart against electrical remodeling and Ica-L remodeling by downregulating CaMKⅡ.
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