%0 Journal Article %T 18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels %A Du Yi-mei %A Xia Cheng-kun %A Zhao Ning %A Dong Qian %A Lei Ming %A Xia Jia-hong %J Acta Pharmacologica Sinica %D 2016 %B 2016 %9 %! 18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels %K %X 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. %U http://www.chinaphar.com/article/view/5636 %V 33 %N 6 %P 752-760 %@ 1745-7254