Astragaloside IV Inhibits Membrane Ca2+ Current but Enhances Sarcoplasmic Reticulum Ca2+ Release

Astragaloside IV (AS-IV) is one of the active ingredients in Astragalus membrananceus (Huangqi), a traditional Chinese medicine. The present study investigated the effects of AS-IV on Ca2+ handling in cardiac myocytes to elucidate its possible mechanism in the treatment of cardiac disease. The results showed that AS-IV at 1 and 10 mu M reduced KCl-induced [Ca2+] i increase (F/F0_ from 1.33 +/- 0.04 (control, n = 28) to 1.22 +/- 0.02 (P < 0.05, n = 29) and 1.22 +/- 0.02 (P < 0.01, n = 20), but it enhanced Ca2+ release from SR (F/ F-0) from 1.04 +/- 0.01 (control, n = 30) to 1.44 +/- 0.03 (P < 0.01, n = 33) and 1.60 +/- 0.04 (P < 0.01, n = 30), in H9c2 cells. Similar results were obtained in native cardiomyocytes. AS-IV at 1 and 10 mu M inhibited L-type Ca2+ current (I-CaL) from 4.42 +/- 0.58 pA/pF of control to 2.25 +/- 0.12 pA/pF (P < 0.01, n = 5) and 1.78 +/- 0.28 pA/pF (P < 0.01, n = 5) respectively, when the interference of [Ca2+] i was eliminated due to the depletion of SR Ca2+ store by thapsigargin, an inhibitor of Ca2+ ATPase. Moreover, when BAPTA, a rapid Ca2+ chelator, was used, CDI (Ca2+-dependent inactivation) of I-CaL was eliminated, and the inhibitory effects of AS-IV on I-CaL were significantly reduced at the same time. These results suggest that AS-IV affects Ca2+ homeostasis through two opposite pathways: inhibition of Ca2+ influx through L-type Ca2+ channel, and promotion of Ca2+ release from SR.