Inhibitory actions of HERG currents by the immunosuppressant drug cyclosporin A

Seung Ho Lee, Sang June Hahn, Gyesik Min, Jimok Kim, Su Hyun Jo, Han Choe, Bok Hee Choi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 IC 50 value and a Hill coefficient of 3.17 μ M 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.

Original languageEnglish (US)
Pages (from-to)291-297
Number of pages7
JournalKorean Journal of Physiology and Pharmacology
Volume15
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • Cyclosporin A
  • HERG
  • Immunosuppressant
  • Long QT syndrome
  • Open channel block

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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