Mutations Leu427, Asn428, and Leu431 Residues within Transmembrane Domain-I-Segment 6 Attenuate Ginsenoside-Mediated L-Type Ca2+ Channel Current Inhibitions
- Mutations Leu427, Asn428, and Leu431 Residues within Transmembrane Domain-I-Segment 6 Attenuate Ginsenoside-Mediated L-Type Ca2+ Channel Current Inhibitions
- 최선혜; 이준호; 표미경; 이병환; 신태준; 황성희; 김보라; 이상목; 오재욱; 김형춘; 배춘식; 임혜원; 나승열
- Panax ginseng; ginsenoside Rg3; L-type Ca2+ channel; site-directed mutation
- Issue Date
- Biological & pharmaceutical bulletin
- VOL 32, NO 7, 1224-1230
- Many lines of evidences have shown that Panax ginseng exhibits beneficial effects on cardiovascular systems.
We previously demonstrated that ginsenoside Rg3 (Rg3), one of active ingredients of Panax ginseng, inhibits Ca2
channel currents in a stereospecific manner and affects the steady-state activation but not inactivation. This
points a possibility that Rg3 regulates Ca2 channels through specific interaction site(s) for Ca2 influx inhibition
through Ca2 channels. However, it was not known how Rg3 interacts with Ca2 channel proteins. In the current
study, we sought to identify these site(s) in Xenopus oocytes expressing cardiac wild-type and mutant L(a1C)-type
Ca2 channels using the two-microelectrode voltage-clamp technique. To this end, we assessed how various point
mutations of the L-type Ca2 channel affected the Rg3 action. Mutations of L427R, N428R and L431K in transmembrane
domain-I-segment 6 (IS6) of the channel significantly attenuated the Rg3 action and caused rightward
shifts in dose–response curves. Rg3 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 Rg3-induced negative shift
of inactivation voltage. Rg3 had no effects on inactivation time constant in wild-type and mutant channels. These
results indicate that Rg3 inhibition of L-type Ca2 channel currents is attenuated by mutations of Leu427,
Asn428 and Leu431 in transmembrane IS6 residues. Leu427, Asn428 and Leu431 residues of the L-type Ca2
channel play important roles in the Rg3 effect on channel properties.
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