In previous reports we have shown that ginsenosides inhibit high threshold voltage-dependent Ca(2+) channels in neuronal cells. However, these studies did not show whether ginsenosides-induced inhibition of Ca(2+) currents discriminates among the various Ca(2+) channel subtypes, although it is known that there are at least five different Ca(2+) channel subtypes in neuronal cells. In this study we investigated the effect of ginsenosides on high threshold voltage-dependent Ca(2+) channel subtypes using their selective Ca(2+) channel blockers nimodipine (L-type), omega-conotoxin GVIA (N-type), or omega-agatoxin IVA (P-type) in bovine chromaffin cells. We could observe that ginsenosides inhibited high threshold voltage-dependent Ca(2+) currents in a dose-dependent manner. The IC(50) was about 120 microgram/ml. Nimodipine had no effect on ginsenosides response. However, the effect of ginsenosides on Ca(2+) currents was reduced by omega-conotoxin GVIA, omega-agatoxin IVA, and mixture of nimodipine, omega-conotoxin GVIA, and omega-agatoxin IVA. These data suggest that ginsenosides are negatively coupled to three types of calcium channels in bovine chromaffin cell, including an omega-conotoxin GVIA-sensitive (N-type) channel, an omega-agatoxin IVA-sensitive (P-type) channel and nimodipine/omega-conotoxin GVIA/omega-agatoxin VIA-resistant (presumptive Q-type) channel. Thus, the selective regulation of voltage-dependent Ca(2+) subtypes by ginsenosides in bovine chromaffin cell could be the cellular basis of antistress effects induced by ginseng.