Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

Abstract

Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus membranaceus, which has various actions on the cardiovascular system. However, its electrophysiological mechanisms are not clear. In the present study, we investigated the effects of AS-IV on action potentials and membrane currents using the whole-cell patch clamp technique in isolated guinea-pig ventricular myocytes. AS-IV prolonged the action potential duration (APD) at all three tested concentrations. The peak effect was achieved with 1×10 −6 m, at which concentration AS-IV significantly prolonged the APD at 95% repolarization from 313.1±38.9 to 785.3±83.7 ms. AS-IV at 1×10 −6 m also enhanced the inward rectifier K + currents (I K1 ) and inhibited the delayed rectifier K + currents (I K ). AS-IV (1×10 −6 m) strongly depressed the peak of voltage-dependent Ca 2+ channel current (I CaL ) from −607.3±37.5 to −321.1±38.3 pA. However, AS-IV was not found to affect the Na + currents. Taken together, AS-IV prolonged APD of guinea-pig ventricular myocytes, which might be explained by its inhibition of I K . AS-IV also influences Ca 2+ signaling through suppressing I CaL .

Electrophysiological effect and the gating mechanism of astragaloside IV on l-type Ca2+ channels of guinea-pig ventricular myocytes

“…Thus these pharmacological effects of AS-IV may be related with its effects on L-type Ca 2 þ channel activity. Previously, we have reported that, AS-IV affects the action potential and one of its effective targets may be the L-type Ca 2 þ channels (Zhao et al, 2013). In the present study, we provided direct evidence that AS-IV affected peak current amplitude of Ca 2 þ current.…”

“…It can be used as potential therapeutic intervention in cardiovascular diseases (Fu et al, 2011(Fu et al, ,2014Yang et al, 2012). AS-IV, one of the major active components of A. membranaceus, is a potent blocker of L-type Ca 2 þ channels in guinea-pig ventricular myocytes (Zhao et al, 2013). In this study, we explored the electrophysiological mechanisms of I CaL inhibition by AS-IV.…”

“…But it remains to be investigated whether the effects of AS-IV on cardiac function are mediated through other calcium regulatory proteins such as L-type Ca 2 þ channels. In our previous work, we have found that AS-IV altered the action potential duration and that one of its targets was the L-type Ca 2 þ channels (Zhao et al, 2013). However, the underlying gating mechanism of AS-IV on cardiac Ca 2 þ channels has not been reported.…”

“…All surgery was performed under sodium pentobarbital anesthesia, and all efforts were made to minimize suffering of the animals. Cardiomyocytes were isolated from left ventricles of guinea-pig (350750 g) hearts, using an enzymatic dissociation method (Zhao et al, 2013). Briefly, the isolated heart was mounted on a Langendorff apparatus and perfused with nominally Ca 2 þ -free Tyrode solution containing collagenase, type I (0.25 mg Á ml À 1 ; Worthington, NJ, USA) at 37 1C.…”

Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3

“…Astragaloside IV, the component of Astragalus membranaceus, exhibits anti-oxidant, anti-cancer and neuro-protective properties [16]. In the current study, we investigated the tumor suppressive effects of astragaloside IV combined with B7-H3 in NSCLC cells.…”