Referenced in: none

Automatically associated channels: Kv1.5 , Kv11.1 , Kv7.1 , Nav1.5

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

Authors: Yi-Mei Du, Cheng-Kun Xia, Ning Zhao, Qian Dong, Ming Lei, Jia-Hong Xia

Journal, date & volume: , 2012 May 21 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22609834

Abstract
To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na(+) current, HERG and Kv1.5 channel currents.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.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.18β-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels.