We investigated the effects of ginseng total saponins (GTS) and five ginsenosides on voltage-dependent Ca2+ channels and membrane capacitance using rat adrenal chromaffin cells. In this study, cells were voltage-clamped in a whole-cell recording mode and a perforated patch-clamp technique was used. The inward Ca2+ currents (I(Ca)) was elicited by depolarization and the change in cell membrane capacitance (deltaCm) was monitored. The application of GTS (100 microg/ml) induced rapid and reversible inhibition of the Ca2+ current by 38.8 +/- 3.6% (n = 16). To identify the particular single component that seems to be responsible for Ca2+ current inhibition, the effects of five ginsenosides (ginsenoside Rb1, Rc, Re, Rf, and Rg1) on the Ca2+ current were examined. The inhibitions to the Ca2+ current by Rb1, Rc, Re, Rf, and Rg1 were 15.3 +/- 2.2% (n = 5); 36.9 +/- 2.4% (n = 7); 28.1 +/- 1.9% (n = 12); 19.0 +/- 2.5% (n = 10); and 16.3 +/- 1.6% (n = 15), respectively. The order of inhibitory potency (100 microM) was Rc > Re > Rf > Rg1 > Rb1. A software based phase detector technique was used to monitor membrane capacitance change (deltaCm). The application of GTS (100 microg/ml) induced inhibitory effects on deltaCm by 60.8 +/- 9.7% (n = 10). The inhibitions of membrane capacitance by Rb1, Rc, Re, Rf, and Rg1 were 35.3 +/- 5.5% (n = 7); 41.8 +/- 7.0% (n = 8); 40.5 +/- 5.9% (n = 9); 51.2 +/- 7.6% (n = 9); and 35.9 +/- 5.1% (n = 10), respectively. The inhibitory potencies of the ginsenosides on deltaCm were Rf > Rc > Re > Rg1 > Rb1. Therefore, we found that GTS and ginsenosides exerted inhibitory effects on both Ca2+ currents and deltaCm in rat adrenal chromaffin cells. These results suggest that ginseng saponins regulate catecholamine secretion from adrenal chromaffin cells and this regulation could be the cellular basis of antistress effects induced by ginseng.