Trachsel D S, Tejada M A, Groesfjeld Christensen V, Pedersen P J, Kanters J K, Buhl R, Calloe K, Klaerke D A
Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
J Vet Pharmacol Ther. 2018 Aug;41(4):536-545. doi: 10.1111/jvp.12502. Epub 2018 Mar 22.
The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction between drugs and potassium channels, especially the K 11.1 channel. Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine. However, some compounds, such as trimethoprim-sulfonamide combinations are still widely used in veterinarian medicine. Therefore, we investigate the effect of trimethoprim-sulfadiazine (TMS), trimethoprim, sulfadiazine, and detomidine on equine-specific K 11.1 channels. K 11.1 channels cloned from equine hearts were heterologously expressed in Xenopus laevis oocytes, and whole cell currents were measured by two-electrode voltage-clamp before and after drug application. TMS blocked equine K 11.1 current with an IC of 3.74 mm (95% CI: 2.95-4.73 mm) and affected the kinetics of activation and inactivation. Similar was found for trimethoprim but not for sulfadiazine, suggesting the effect is due to trimethoprim. Detomidine did not affect equine K 11.1 current. Thus, equine K 11.1 channels are also susceptible to pharmacological block, indicating that some drugs may have the potential to affect repolarization in horse. However, in vivo studies are needed to assess the potential risk of these drugs to induce equine LQTS.
长QT综合征（LQTS）是一种通道病，可导致严重心律失常和心源性猝死。药物诱导的LQTS是由药物与钾通道，尤其是K 11.1通道之间的相互作用引起的。由于这种相互作用，许多药物已从市场上撤出或在人类医学中谨慎使用。然而，一些化合物，如甲氧苄啶-磺胺类药物组合仍广泛用于兽医学。因此，我们研究了甲氧苄啶-磺胺嘧啶（TMS）、甲氧苄啶、磺胺嘧啶和右美托咪定对马特异性K 11.1通道的影响。从马心脏克隆的K 11.1通道在非洲爪蟾卵母细胞中进行异源表达，并在施加药物前后通过双电极电压钳测量全细胞电流。TMS以3.74毫米（95%置信区间：2.95-4.73毫米）的半数抑制浓度阻断马K 11.1电流，并影响激活和失活动力学。甲氧苄啶也有类似情况，但磺胺嘧啶没有，这表明该作用是由甲氧苄啶引起的。右美托咪定不影响马K 11.1电流。因此，马K 11.1通道也易受药物阻断，这表明一些药物可能有影响马复极化的潜力。然而，需要进行体内研究来评估这些药物诱发马LQTS的潜在风险。
