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

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D. S. Trachsel, M. A. Tejada, V. Groesfjeld Christensen, P. J. Pedersen, J. K. Kanters, R. Buhl, K. Calloe, D. A. Klaerke

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 Kv11.1 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 Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine.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 Kv11.1 channels. Kv11.1 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 Kv11.1 current with an IC50 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 Kv11.1 current. Thus, equine Kv11.1 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.

Original languageEnglish
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume41
Issue number4
Pages (from-to)536-545
Number of pages10
ISSN0140-7783
DOIs
Publication statusPublished - 2018

    Research areas

  • acquired LQTS, heart, hERG, potassium channels, Repolarization

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