Dataset Information

18?-Glycyrrhetinic acid preferentially blocks late Na current generated by ?KPQ Nav1.5 channels.

ABSTRACT:

Aim

To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na(+) current, HERG and Kv1.5 channel currents.

Methods

Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant ?KPQ Nav1.5 channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes. In addition, isolated human atrial myocytes were used. Two-microelectrode voltage-clamp technique was used to record the voltage-activated currents.

Results

Superfusion of 18?-glycyrrhetinic acid (18?-GA, 1-100 ?mol/L) blocked both the peak current (I(Na,P)) and late current (I(Na,L)) generated by WT and ?KPQ Nav1.5 channels in a concentration-dependent manner, while 18?-glycyrrhetinic acid (18?-GA) at the same concentrations had no effects. 18?-GA preferentially blocked I(Na,L) (IC(50)=37.2 ± 14.4 ?mol/L) to I(Na,P) (IC(50)=100.4 ± 11.2 ?mol/L) generated by ?KPQ Nav1.5 channels. In human atrial myocytes, 18?-GA (30 ?mol/L) inhibited 47% of I(Na,P) and 87% of I(Na,L) induced by Anemonia sulcata toxin (ATX-II, 30 nmol/L). Superfusion of 18?-GA (100 ?mol/L) had no effects on HERG and Kv1.5 channel currents.

Conclusion

18?-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels.

SUBMITTER: Du YM

PROVIDER: S-EPMC4010371 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels.

Du Yi-mei YM Xia Cheng-kun CK Zhao Ning N Dong Qian Q Lei Ming M Xia Jia-hong JH

Acta pharmacologica Sinica 20120521 6

<h4>Aim</h4>To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na(+) current, HERG and Kv1.5 channel currents.<h4>Methods</h4>Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant ΔKPQ Nav1.5 channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes. In addition, isolated human atrial myocytes were used. Two-microelectrode voltage-clamp technique was used to record the voltage-activated currents.<h4>Results</h4>Superfusio ...[more]

PMID: 22609834

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