title: KN-93 inhibits IKr in mammalian cardiomyocytes.
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.
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, USA.
authors.forename: Bence
authors.initials: B
authors.lastname: Hegyi
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, USA; Department of Biomedical Engineering, University of California, Davis, CA USA; Department of Internal Medicine (Cardiology), University of California, Davis, CA USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen-Izu
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Jian
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, USA; Department of Biomedical Engineering, University of California, Davis, CA USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Shimkunas
authors.affiliation: Department of Pharmacology, University of California, Davis, CA, USA.
authors.forename: Leighton T
authors.initials: LT
authors.lastname: Izu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Electronic address: banyasz.tamas@med.unideb.hu.
authors.forename: Tamas
authors.initials: T
authors.lastname: Banyasz
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D006168:Guinea Pigs; D008322:Mammals / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D015221:Potassium Channels; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides
keywords: CaMKII; I(Kr); KN-93; Off target effect; Pharmacology; Ventricular myocytes