KN-93 inhibits IKr in mammalian cardiomyocytes

Bence Hegyi, Ye Chen-Izu, Zhong Jian, Rafael Shimkunas, Leighton T Izu, Tamas Banyasz

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 is widely used in multiple fields of cardiac research especially for studying the mechanisms of cardiomyopathy and cardiac arrhythmias. Whereas KN-93 is a potent inhibitor of CaMKII, several off-target effects have also been found in expression cell systems and smooth muscle cells, but there is no information on the KN93 side effects in mammalian ventricular myocytes. In this study we explore the effect of KN-93 on the rapid component of delayed rectifier potassium current (IKr) in the ventricular myocytes from rabbit and guinea pig hearts. Our data indicate that KN-93 exerts direct inhibitory effect on IKr that is not mediated via CaMKII. This off-target effect of KN93 should be taken into account when interpreting the data from using KN93 to investigate the role of CaMKII in cardiac function.

Original languageEnglish (US)
Pages (from-to)173-176
Number of pages4
JournalJournal of Molecular and Cellular Cardiology
Volume89
DOIs
StatePublished - Dec 1 2015

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Keywords

  • CaMKII
  • I
  • KN-93
  • Off target effect
  • Pharmacology
  • Ventricular myocytes

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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