The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state

• Published in: The Korean journal of physiology & pharmacology Vol. 26; no. 2; pp. 135 - 144
• Main Authors: Lee, Hyang Mi, Hahn, Sang June, Choi, Bok Hee
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Physiological Society and The Korean Society of Pharmacology 01.03.2022; 대한약리학회
• Subjects: Original; 약리학; Open channel block; Rosiglitazone; Kv1.5 channel; Cardiotoxicity; Ion channel
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2022.26.2.135

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 concentration-dependent manner (IC = 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 use-dependence 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.