Abstract

Astragaloside IV (AGS-IV), a traditional Chinese herb, has been found to have potent cardioprotective effects. However, the relevant mechanisms still remain unclear. In the present study, using standard whole-cell patch clamp recording technique, we identified a novel functional role of AGS-IV in regulating L-type calcium channel currents (L-currents) in adult rat ventricular myocytes. Our results showed that AGS-IV exerted inhibitory effects on L-currents of the single adult rat ventricular myocytes. This L-current inhibitory action of AGS-IV was concentration-dependent. The current density at +10 mV was reduced by about 48.7% after exposure of the cells to AGS-IV (1 µM), from the control value of 13.7±1.7 to 7.6±1.2 pA/pF. AGS-IV did not markedly affect the activation of L-currents but significantly shifted the inactivation curve to the left. Pretreatment of cells with H89, a protein kinase A (PKA) inhibitor, completely abolished AGS-IV-induced L-current inhibition. Similar results were obtained by another PKA inhibitor PKI 5-24. Taken together, these results suggested that AGS-IV inhibited L-currents via a PKA-dependent pathway in rat ventricular myocytes, which could contribute to its cardioprotective effects.

Key words: Astragaloside IV, L-type calcium channels, ventricular myocytes, patch clamp.