Effect of ginsenosides on voltage-dependent Ca 2+ channel subtypes in bovine chromaffin cells

Abstract

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), ω-conotoxin GVIA (N-type), or ω-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 μg/ml. Nimodipine had no effect on ginsenosides response. However, the effect of ginsenosides on Ca 2+ currents was reduced by ω-conotoxin GVIA, ω-agatoxin IVA, and mixture of nimodipine, ω-conotoxin GVIA, and ω-agatoxin IVA. These data suggest that ginsenosides are negatively coupled to three types of calcium channels in bovine chromaffin cell, including an ω-conotoxin GVIA-sensitive (N-type) channel, an ω-agatoxin IVA-sensitive (P-type) channel and nimodipine/ω-conotoxin GVIA/ω-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.