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Updated: Aug 13, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
U50488 inhibits outwardly rectifying potassium channel in PC12 cells via pertussis toxin-sensitive G-protein
Zhisong Li1, Lei Guo, Caiying Ye
1Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Abstract:
This study was undertaken to determine the effect of U50488, a kappa-opioid receptor agonist, on outwardly rectifying potassium channel (Ik) in undifferentiated PC12 cells. Using whole-cell and on-cell patch-clamp techniques, we found that U50488 decreased Ik amplitude in a time-dependent manner and Ik activation was delayed. Single-channel kinetic analysis provided a two-stage model for us to illuminate the blockage effect induced by U50488. To identify whether U50488 mediates the effect through opioid receptor and G-protein, several specific blockers and activators were used. Not only naloxone but also PTX and GDPbetaS abolished U50488-induced suppression; however, such effect was not observed when cAMP or other adenylyl cyclase activators were used. It is postulated that kappa-opioid receptor and Gi/o protein, but not cAMP, are involved in U50488-induced suppression of Ik.
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