Details

Autor(en) / Beteiligte

• Li, Yifu
• Tu, Danna
• Xiao, Hua
• Du, Yimei
• Zou, Anruo
• Liao, Yuhua
• Dong, Shaohong

Titel

Aconitine blocks HERG and Kv1.5 potassium channels

Ist Teil von

• Journal of ethnopharmacology, 2010-08, Vol.131 (1), p.187-195

Ort / Verlag

Shannon: Elsevier Ireland Ltd

Erscheinungsjahr

2010

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Aconitine (ACO) is a classic drug of arrhythmogenic agents for establishment of arrhythmias in animal models. We used a two-microelectrode voltage-clamp technique analysis of Kv1.5 and HERG channels expressed in Xenopus laevis oocytes to characterize the blocking activity of ACO. Aconitum has been widely used to treat various diseases in China for a long time. However, improper use of this drug results in severe intoxication. Aconitine (ACO), a diterpenoid alkaloid from aconitum, mainly contributes to cardio-toxic effects of aconitum and has also been commonly known to induce arrhythmias in animal models. However, its pro-arrhythmic mechanisms are not clear. The effects of ACO on HERG and Kv1.5 channels were investigated. HERG and Kv1.5 channels were expressed in Xenopus laevis oocytes, and the resulting currents were recorded using a two-microelectrode voltage clamp technique. In HERG channels, ACO exhibited a blockade in a voltage- and time-dependent manner. The blockade was enhanced by further activation of currents, which were consistent with an open-channel blockade. In Kv1.5 channels, ACO produced a voltage-, time-, and frequency-dependent inhibition. The blockade was enhanced by higher rates of stimulation, consistent with preferential binding of the drug to the open state. In addition, ACO blocked Kv1.5 and HERG channels in a concentration-dependent manner with an IC 50 of 0.796 ± 0.123 and 1.801 ± 0.332 μM, respectively. ACO blocks HERG and Kv1.5 potassium channels in the open state. Blockade of potassium channels, particular the HERG channel, may be one of the important mechanisms of how ACO induces arrhythmias.