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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 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. RESULTS: Superfusion of 18β-glycyrrhetinic acid (18β-GA, 1-100 μmol/L) blocked both the peak current (I(Na,P)) and late current (I(Na,L)) generated by WT and ΔKPQ Nav1.5 channels in a concentration-dependent manner, while 18α-glycyrrhetinic acid (18α-GA) at the same concentrations had no effects. 18β-GA preferentially blocked I(Na,L) (IC(50)=37.2 ± 14.4 μmol/L) to I(Na,P) (IC(50)=100.4 ± 11.2 μmol/L) generated by ΔKPQ Nav1.5 channels. In human atrial myocytes, 18β-GA (30 μmol/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 18β-GA (100 μmol/L) had no effects on HERG and Kv1.5 channel currents. CONCLUSION: 18β-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels.

Original publication

DOI

10.1038/aps.2012.22

Type

Journal

Acta Pharmacol Sin

Publication Date

06/2012

Volume

33

Pages

752 - 760

Keywords

Animals, Cells, Cultured, ERG1 Potassium Channel, Ether-A-Go-Go Potassium Channels, Gene Expression, Glycyrrhetinic Acid, Humans, Kv1.5 Potassium Channel, Long QT Syndrome, Mutation, Myocytes, Cardiac, NAV1.5 Voltage-Gated Sodium Channel, Oocytes, Patch-Clamp Techniques, Sodium, Sodium Channels, Stereoisomerism, Xenopus