Inhibitory Actions of HERG Currents by the Immunosuppressant Drug Cyclosporin A

• Published in: The Korean journal of physiology & pharmacology Vol. 15; no. 5; pp. 291 - 297
• Main Authors: Lee, Seung Ho, Hahn, Sang June, Min, Gyesik, Kim, Jimok, Jo, Su-Hyun, Choe, Han, Choi, Bok Hee
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Physiological Society and The Korean Society of Pharmacology 01.10.2011; 대한약리학회
• Subjects: Original; 약리학; Long QT syndrome; Open channel block; Immunosuppressant; HERG; Cyclosporin A
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2011.15.5.291

The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an IC(50) value and a Hill coefficient of 3.17 µM and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.