Inhibitory effects of isoliquiritigenin and licorice extract on voltage-dependent K(+) currents in H9c2 cells.
The effect of isoliquiritigenin (ISL), a component of licorice, on the voltage-dependent, ultra-rapidly activating delayed-rectifier K(+) current (IKur) was examined in H9c2 cells, a cell-line derived from rat cardiac myoblasts. IKur was recorded using the whole-cell patch clamp method with a pipette solution containing 140 mM K(+). Depolarizing voltage pulses of 200-ms duration were given with 10-mV steps every 10 s from -40 mV holding potential. ISL inhibited IKur in a concentration-dependent manner. The median inhibitory concentration (IC(50)) of ISL was approximately 0.11 microM and the Hill coefficient was 0.71. Using CHO cells expressing Kv1.5 IKur channels, ISL also inhibited Kv1.5 IKur, but less potently than the IKur current in H9c2 cells. Furthermore, in H9c2 cells, the licorice extract itself inhibited IKur in a manner similar to ISL. We conclude that ISL, one component of licorice, is a potent inhibitor of K(+) channels, which specifically in H9c2 cells could be Kv2.1, and that this inhibition may be involved in various pharmacological effects of licorice.
Noguchi
Chisato
C
Department of Anesthesiology, Fukushima Medical University, School of Medicine, Japan.
Yang
Jing
J
Sakamoto
Kazuho
K
Maeda
Ryo
R
Takahashi
Kenji
K
Takasugi
Hiroshi
H
Ono
Tomoyuki
T
Murakawa
Masahiro
M
Kimura
Junko
J
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D047188:Chalcones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats
D047188:Chalcones; D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D026902:Potassium Channel Blockers; C040920:isoliquiritigenin