Many lines of evidences have shown that
Panax ginseng exhibits beneficial effects on cardiovascular systems. We previously demonstrated that ginsenoside Rg
3 (Rg
3), one of active ingredients of
Panax ginseng, inhibits Ca
2+ channel currents in a stereospecific manner and affects the steady-state activation but not inactivation. This points a possibility that Rg
3 regulates Ca
2+ channels through specific interaction site(s) for Ca
2+ influx inhibition through Ca
2+ channels. However, it was not known how Rg
3 interacts with Ca
2+ channel proteins. In the current study, we sought to identify these site(s) in
Xenopus oocytes expressing cardiac wild-type and mutant L(α
1C)-type Ca
2+ channels using the two-microelectrode voltage-clamp technique. To this end, we assessed how various point mutations of the L-type Ca
2+ channel affected the Rg
3 action. Mutations of L427R, N428R and L431K in transmembrane domain-I-segment 6 (IS6) of the channel significantly attenuated the Rg
3 action and caused rightward shifts in dose–response curves. Rg
3 treatment produced a negative shift in the inactivation voltage but did not alter the steady-state activation voltage, and none of the mutant channels affected the Rg
3-induced negative shift of inactivation voltage. Rg
3 had no effects on inactivation time constant in wild-type and mutant channels. These results indicate that Rg
3 inhibition of L-type Ca
2+ channel currents is attenuated by mutations of Leu427, Asn428 and Leu431 in transmembrane IS6 residues. Leu427, Asn428 and Leu431 residues of the L-type Ca
2+ channel play important roles in the Rg
3 effect on channel properties.
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