Green tea flavonoid epigallocatechin-3-gallate (EGCG) inhibits cardiac hERG potassium channels.
The catechin EGCG is the main flavonoid compound of green tea and has received enormous pharmacological attention because of its putative beneficial health effects. This study investigated for the first time the effect of EGCG on hERG channels, the main pharmacological target of drugs that cause acquired long QT syndrome. Cloned hERG channels were expressed in Xenopus oocytes and in HEK293 cells. Heterologous hERG currents were inhibited by EGCG with an IC50 of 6.0 micromol/l in HEK293 cells and an IC50 of 20.5 micromol/l in Xenopus laevis oocytes. Onset of effect was slow and only little recovery from inhibition was observed upon washout. In X. laevis oocytes EGCG inhibited hERG channels in the open and inactivated states, but not in the closed states. The half-maximal activation voltage of hERG currents was shifted by EGCG towards more positive potentials. In conclusion, EGCG is a low-affinity inhibitor of hERG sharing major electrophysiological features with pharmaceutical hERG antagonists.
Kelemen
Kamilla
K
Department of Internal Medicine III-Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. kamilla_kelemen@web.de
Kiesecker
Claudia
C
Zitron
Edgar
E
Bauer
Alexander
A
Scholz
Eberhard
E
Bloehs
Ramona
R
Thomas
Dierk
D
Greten
Johannes
J
Remppis
Andrew
A
Schoels
Wolfgang
W
Katus
Hugo A
HA
Karle
Christoph A
CA
D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D013662:Tea / Q000737:chemistry*; D014982:Xenopus laevis
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D011188:Potassium