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.
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.
Authors: Nathalie H Nielsen; Bo G Winkel; Jørgen K Kanters; Nicole Schmitt; Jacob Hofman-Bang; Henrik S Jensen; Bo H Bentzen; Bjarne Sigurd; Lars A Larsen; Paal S Andersen; Stig Haunsø; Keld Kjeldsen; Morten Grunnet; Michael Christiansen; Søren-Peter Olesen Journal: Biochem Biophys Res Commun Date: 2007-01-18 Impact factor: 3.575
Authors: Sharon L Hale; John C Shryock; Luiz Belardinelli; Michael Sweeney; Robert A Kloner Journal: J Mol Cell Cardiol Date: 2008-04-08 Impact factor: 5.000
Authors: Béla Völgyi; Feng Pan; David L Paul; Jack T Wang; Andrew D Huberman; Stewart A Bloomfield Journal: PLoS One Date: 2013-07-23 Impact factor: 3.240