PMID- 26463508
OWN - NLM
STAT- MEDLINE
DCOM- 20160926
LR  - 20240213
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 89
IP  - Pt B
DP  - 2015 Dec
TI  - KN-93 inhibits IKr in mammalian cardiomyocytes.
PG  - 173-6
LID - S0022-2828(15)30083-3 [pii]
LID - 10.1016/j.yjmcc.2015.10.012 [doi]
AB  - 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.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Hegyi, Bence
AU  - Hegyi B
AD  - Department of Pharmacology, University of California, Davis, CA, USA.
FAU - Chen-Izu, Ye
AU  - Chen-Izu Y
AD  - 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.
FAU - Jian, Zhong
AU  - Jian Z
AD  - Department of Pharmacology, University of California, Davis, CA, USA.
FAU - Shimkunas, Rafael
AU  - Shimkunas R
AD  - Department of Pharmacology, University of California, Davis, CA, USA; Department 
      of Biomedical Engineering, University of California, Davis, CA USA.
FAU - Izu, Leighton T
AU  - Izu LT
AD  - Department of Pharmacology, University of California, Davis, CA, USA.
FAU - Banyasz, Tamas
AU  - Banyasz T
AD  - Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary. Electronic address: banyasz.tamas@med.unideb.hu.
LA  - eng
GR  - R01 HL090880/HL/NHLBI NIH HHS/United States
GR  - T32 HL086350/HL/NHLBI NIH HHS/United States
GR  - R03 AG031944/AG/NIA NIH HHS/United States
GR  - R01 HL123526/HL/NHLBI NIH HHS/United States
GR  - R01HL90880/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151014
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Benzylamines)
RN  - 0 (Potassium Channels)
RN  - 0 (Sulfonamides)
RN  - 139298-40-1 (KN 93)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Benzylamines/*pharmacology
MH  - Guinea Pigs
MH  - Mammals/*metabolism
MH  - Myocytes, Cardiac/drug effects/*metabolism
MH  - Patch-Clamp Techniques
MH  - Potassium Channels/*metabolism
MH  - Rabbits
MH  - Sulfonamides/*pharmacology
PMC - PMC4689637
MID - NIHMS736416
OTO - NOTNLM
OT  - CaMKII
OT  - I(Kr)
OT  - KN-93
OT  - Off target effect
OT  - Pharmacology
OT  - Ventricular myocytes
EDAT- 2015/10/16 06:00
MHDA- 2016/09/27 06:00
PMCR- 2016/12/01
CRDT- 2015/10/15 06:00
PHST- 2015/08/08 00:00 [received]
PHST- 2015/10/08 00:00 [revised]
PHST- 2015/10/09 00:00 [accepted]
PHST- 2015/10/15 06:00 [entrez]
PHST- 2015/10/16 06:00 [pubmed]
PHST- 2016/09/27 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - S0022-2828(15)30083-3 [pii]
AID - 10.1016/j.yjmcc.2015.10.012 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2015 Dec;89(Pt B):173-6. doi: 10.1016/j.yjmcc.2015.10.012. 
      Epub 2015 Oct 14.