The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state

  • Lee, Hyang Mi (Department of Pharmacology, Institute for Medical Sciences, Jeonbuk National University Medical School) ;
  • Hahn, Sang June (Department of Physiology, Medical Research Center, College of Medicine, The Catholic University of Korea) ;
  • Choi, Bok Hee (Department of Pharmacology, Institute for Medical Sciences, Jeonbuk National University Medical School)
  • Received : 2022.01.03
  • Accepted : 2022.01.17
  • Published : 2022.03.01
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Abstract

An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentrationdependent manner (IC50 = 18.9 μM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the usedependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics.

Keywords

Acknowledgement

We thank Dr. Leonard Kaczmarek (Yale University School of Medicine, USA) for the rat Kv1.5 cDNA.

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