Korean J Physiol Pharmacol.  2023 Jan;27(1):95-103. 10.4196/kjpp.2023.27.1.95.

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

• Lee HM
• Yoon SH
• Kim MG
• Hahn SJ
• Choi BH

• KMID: 2537507
• DOI: http://doi.org/10.4196/kjpp.2023.27.1.95

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.

Keyword

Open channel block; Potassium channels; Rosiglitazone; Shaw-type potassium channels