Inhibitory Actions of HERG Currents by the Immunosuppressant Drug Cyclosporin A.
10.4196/kjpp.2011.15.5.291
- Author:
Seung Ho LEE
1
;
Sang June HAHN
;
Gyesik MIN
;
Jimok KIM
;
Su Hyun JO
;
Han CHOE
;
Bok Hee CHOI
Author Information
1. Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 561-180, Korea. bhchoi@jbnu.ac.kr
- Publication Type:Original Article
- Keywords:
Cyclosporin A;
Immunosuppressant;
HERG;
Long QT syndrome;
Open channel block
- MeSH:
Calcineurin;
Cyclosporine;
Humans;
Inhibitory Concentration 50;
Kidney;
Long QT Syndrome;
Patch-Clamp Techniques
- From:The Korean Journal of Physiology and Pharmacology
2011;15(5):291-297
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 IC50 value and a Hill coefficient of 3.17 microM 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.
