Ephedrine controls heart rhythms by activating cardiac I(ks) currents.
Ephedrine (Eph) is an alkaloid extracted from the Chinese traditional medicine plant Ephedra Sinica or Ma huang, which has been known for effects on the central nervous system, cardiovascular system, and smooth muscles. However, the corresponding molecular mechanism of these effects remains unknown. In this study, we investigated the influences of Eph on heart rate, QTc interval in vivo, and the slowly activated K channels (IKs) that were composed of both KCNQ1 and KCNE1 subunits in vitro. Results demonstrated that Eph, but not pseudoephedrine, could increase the heart rate and shorten QTc interval of BALB/c mouse. Besides, Eph markedly activated cardiac IKs currents with EC50 = 50 nM and shifted G-V curves to left. But pseudoephedrine had no effects on Iks currents. The onset and offset time constants of IKs currents activated by Eph at 1 M were tauon = 49 seconds and tauoff = 400 seconds. A pair of binding sites of Eph on KCNQ1/KCNE1 channel was also shown to occur at F296 and Y299 in the S5-S6 P-loop of the KCNQ1 channel. As both amino acids are highly conserved in the KCNQ family, Eph can possibly activate other members of the KCNQ family. The mechanism of Iks activated by Eph may provide a clue for drug design in the future.
Jing
Hongjuan
H
Huazhong University of Science and Technology, Wuhan, Hubei, China.
Luo
Lan
L
Li
Hui
H
Sun
Jing
J
Yi
Hong
H
Wu
Yingliang
Y
Wang
Changdong
C
He
Guangyuan
G
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004809:Ephedrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000737:chemistry / Q000378:metabolism; D008133:Long QT Syndrome / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
D051657:KCNQ1 Potassium Channel; C092068:Kcne1 protein, mouse; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); D004809:Ephedrine