Blockade of K+ and Ca2+ channels by azole antifungal agents in neonatal rat ventricular myocytes

Dong Jun Sung, Jae Gon Kim, Kyung Jong Won, Bokyung Kim, Ho Chul Shin, Jae Yong Park, Young Min Bae

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Some azole antifungal agents induce long QT syndrome and arrhythmias. Although composite functions of ion channels in cardiomyocytes contribute to the shaping of action potentials, information on the effects of azole antifungal agents on ion currents, except human-ether-a-go-go-related gene (HERG) K + currents, is largely lacking. Using the whole cell patch-clamp technique, we investigated the effects of four azole agents (miconazole, ketoconazole, fluconazole, and itraconazole) on inward rectifying K+ currents (IKir), voltage-gated L-type Ca2+ currents (ICaL), and delayed rectifier K+ currents (IK dr) in rat neonate ventricular myocytes. Strikingly, miconazole and ketoconazole strongly inhibited IKir, IKdr, and ICa L at clinically relevant concentrations. The IC50 values of miconazole for IKdr, IKir, and ICaL inhibition were 2.5, 10.4, and 3.0 μM, respectively. The IC50 values of ketoconazole for IKdr, IKir and ICaL inhibition were 3.2, 20.8, and 3.5 μM, respectively. Fluconazole and itraconazole had relatively little effect on ion currents. These findings indicate that miconazole and ketoconazole are multiple ion channel inhibitors in cardiomyocytes. We suggest that it is necessary to consider this inhibition of ion channels by azole agents when assessing cardiovascular side effects.

Original languageEnglish
Pages (from-to)1469-1475
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume35
Issue number9
DOIs
Publication statusPublished - 2012 Sep
Externally publishedYes

Keywords

  • Arrhythmia
  • Azole antifungal agent
  • Neonate rat cardiomyocyte

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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