Effects of trimethoprim–sulfadiazine and detomidine on the function of equine Kv11.1 channels in a two‐electrode voltage‐clamp (TEVC) oocyte model

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 v 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 Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine.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 v 11.1 channels. K v 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 v 11.1 current with an IC 50 of 3.74 m m (95% CI: 2.95–4.73 m m ) 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 v 11.1 current. Thus, equine K v 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.