Glycyrretinic acid blocks cardiac sodium channels expressed in Xenopus oocytes.
BACKGROUND
Licorice has been used to treat many ailments including cardiovascular disorders in China for long time. Recent studies have shown that the cardiac actions of licorice have been attributed to its active component, glycyrretinic acid (GA). However, its mechanism remains poorly understood.


OBJECTIVE
The effects of GA on the cardiac sodium currents (I(Na)), L-type calcium currents (I(Ca,L)) and hyperpolarization-activated inward currents (I(f)) were investigated.


METHODS
Human isoforms of wild-type and DeltaKPQ-mutant type sodium channels were expressed in Xenopus oocytes, and the resulting currents (peak and late I(Na)) were recorded using a two-microelectrode voltage-clamp technique. A perforated patch clamp technique was employed to record I(Ca,L) and I(f) from isolated rabbit sinoatrial node pacemaker cells.


RESULTS
GA inhibited peak I(Na) (33% at 90 microM) and late I(Na) (72% at 90 microM), but caused no significant effects on I(Ca,L) and I(f).


CONCLUSIONS
GA blocked cardiac sodium currents, particularly late I(Na.) Our findings might help to understand the traditional use of licorice in the treatment of cardiovascular disorders, because reduction of sodium currents (particularly late I(Na)) would be expected to provide protection from Na(+)-induced Ca(2+) overload and cell damage.
Du
Yimei
Y
Ion Channelopathy Research Center, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Zhang
Songyu
S
Wu
Hongjin
H
Zou
Anruo
A
Lei
Ming
M
Cheng
Longxian
L
Liao
Yuhua
Y
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis
D020746:Calcium Channels, L-Type; D010936:Plant Extracts; D015222:Sodium Channels; D012964:Sodium; D006034:Glycyrrhetinic Acid; D002118:Calcium