Effects of rosiglitazone, an antidiabetic drug, on Kv3.1 channels
10.4196/kjpp.2023.27.1.95
- Author:
Hyang Mi LEE
1
;
Seong Han YOON
;
Min-Gul KIM
;
Sang June HAHN
;
Bok Hee CHOI
Author Information
1. Department of Pharmacology, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju 54097, Korea
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2023;27(1):95-103
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC 50 = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated 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.
