Effects of rosiglitazone, an antidiabetic drug, on Kv3.1 channels

• Published in: The Korean journal of physiology & pharmacology 2023-01, Vol.27 (1), p.95-103
• Main Authors: Lee, Hyang Mi, Yoon, Seong Han, Kim, Min-Gul, Hahn, Sang June, Choi, Bok Hee
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2023.27.1.95

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the whole-cell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC = 29.8 μM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazone-mediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.