Effects of Ginsenoside Rg₃ on α9α10 Nicotinic Acetylcholine Receptor-Mediated Ion Currents

抄録

Ginsenosides is a low molecular weight substance found in ginseng as one of the active ingredients. Ginsenosides, like other herbal medicines, has a wide range of neuropharmacological actions including neuroprotective effects. The α9α10 nicotinic acetylcholine receptor is one of numerous nicotinic acetylcholine receptors that exists as a heteropentameric form in auditory hair cells of the cochlea. In this study, we report the effects of ginsenosides on rat α9α10 nicotinic acetylcholine receptor-mediated ion currents using the two-electrode voltage clamp technique. Treatment with acetylcholine evoked inward currents (I_ACh) in oocytes heterologously expressing the α9α10 nicotinic acetylcholine receptor. Ginsenosides blocked I_ACh in order of potency of Rg₃> Rb₂> CK>Re=Rg₂> Rf>Rc> Rb₁> Rg₁ with reversible manners, and the blocking effect of Rg₃ on I_ACh was same after pre-application than co-application of Rg₃. The half maximal inhibitory concentration (IC₅₀) of Rg₃ was 39.6±4.9 µm. Rg₃-induced I_ACh inhibition was not affected by acetylcholine concentration and was independent of membrane holding potential. Although the inhibitory effect of Rg₃ on I_ACh was abolished in oocytes expressing α9 subunit alone, indicating that the presence of α10 subunit might be required for Rg₃-induced regulations of α9α10 nicotinic acetylcholine receptor channel activity. These results indicate that α10 subunit of α9α10 nicotinic acetylcholine receptor might play an important role in Rg₃-induced regulation of the α9α10 nicotinic acetylcholine receptor.