![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 290, Issue 3, 1165-1174, September 1999
Department of Physiology, University of Montreal, and Research
Centre, Montreal Heart Institute, Montreal, Canada
The present study was undertaken to investigate the effects of specific
inhibitors of calmodulin-dependent protein kinase II (CamKII) on
macroscopic voltage-dependent K+ current (KV)
recorded from rabbit portal vein smooth muscle cells. Inhibition of
L-type Ca2+ current facilitation by 1 µM KN-62, a blocker
of CamKII, was first demonstrated and provided evidence for functional
CamKII activity in this preparation. KN-93, another specific and more potent inhibitor of CamKII in the rat brain, suppressed KV
and enhanced the rate of inactivation in a dose-dependent manner, in
cells dialyzed with both low (0.1 mM) and high (10 mM) EGTA pipette
solution. Prolonged dialysis with 10 µM of a synthetic peptide
inhibitor of CamKII (fragment 281-301) had little effect on
KV and did not prevent the inhibitory action of KN-93 on
the current. The estimated IC50 for inhibiting peak and
late currents during 250-ms steps to +60 mV (holding potential = 
60 mV) were 2.9 and 0.27 µM, respectively. KN-93 also induced
slight shifts of the steady-state activation (7 mV) and inactivation
(6 mV) curves. KN-62, and KN-92, an inactive analog of KN-93,
produced effects similar to those of KN-93. In current clamp
experiments, 5 µM KN-93 depolarized the myocytes from a control
resting membrane potential of 42.3 ± 2.8 mV to 28.5 ± 1.4 mV, an effect that was partially reversible after washout
(34.4 ± 1.3 mV, n = 6). In conclusion,
blockers of CamKII produce nonspecific inhibitory effects on
KV that warrant cautious use of these compounds in physiological experiments designed to assess the role of CamKII.
This article has been cited by other articles:
|
|
 |
|
  Y. Wu, Z. Gao, B. Chen, O. M. Koval, M. V. Singh, X. Guan, T. J. Hund, W. Kutschke, S. Sarma, I. M. Grumbach, et al. From the Cover: Calmodulin kinase II is required for fight or flight sinoatrial node physiology PNAS, April 7, 2009; 106(14): 5972 - 5977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xiao, P. Coutu, L. R. Villeneuve, A. Tadevosyan, A. Maguy, S. Le Bouter, B. G. Allen, and S. Nattel Mechanisms Underlying Rate-Dependent Remodeling of Transient Outward Potassium Current in Canine Ventricular Myocytes Circ. Res., September 26, 2008; 103(7): 733 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, S. Tandan, J. Cheng, C. Yang, L. Nguyen, J. Sugianto, J. L. Johnstone, Y. Sun, and J. A. Hill Ca2+/Calmodulin-dependent Protein Kinase II-dependent Remodeling of Ca2+ Current in Pressure Overload Heart Failure J. Biol. Chem., September 12, 2008; 283(37): 25524 - 25532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Martin, N. Boucher, C. Brousseau, and J. J. Tremblay The Orphan Nuclear Receptor NUR77 Regulates Hormone-Induced StAR Transcription in Leydig Cells through Cooperation with Ca2+/Calmodulin-Dependent Protein Kinase I Mol. Endocrinol., September 1, 2008; 22(9): 2021 - 2037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Vest, K. D. Davies, H. O'Leary, J. D. Port, and K. U. Bayer Dual Mechanism of a Natural CaMKII Inhibitor Mol. Biol. Cell, December 1, 2007; 18(12): 5024 - 5033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Liu, B. Chen, Q. Ge, and Z.-W. Wang Presynaptic Ca2+/Calmodulin-Dependent Protein Kinase II Modulates Neurotransmitter Release by Activating BK Channels at Caenorhabditis elegans Neuromuscular Junction J. Neurosci., September 26, 2007; 27(39): 10404 - 10413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Mu, L. D. Brown, Y. Liu, and M. F. Schneider Roles of the calcineurin and CaMK signaling pathways in fast-to-slow fiber type transformation of cultured adult mouse skeletal muscle fibers Physiol Genomics, August 20, 2007; 30(3): 300 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Qu, V. E. Bondarenko, C. Xie, S. Wang, M. S. Awayda, H. C. Strauss, and M. J. Morales W-7 modulates Kv4.3: pore block and Ca2+-calmodulin inhibition Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2364 - H2377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Colinas, M. Gallego, R. Setien, J. R. Lopez-Lopez, M. T. Perez-Garcia, and O. Casis Differential modulation of Kv4.2 and Kv4.3 channels by calmodulin-dependent protein kinase II in rat cardiac myocytes Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1978 - H1987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S.C. Khoo, J. Li, M. V. Singh, Y. Yang, P. Kannankeril, Y. Wu, C. E. Grueter, X. Guan, C. V. Oddis, R. Zhang, et al. Death, Cardiac Dysfunction, and Arrhythmias Are Increased by Calmodulin Kinase II in Calcineurin Cardiomyopathy Circulation, September 26, 2006; 114(13): 1352 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rezazadeh, T. W. Claydon, and D. Fedida KN-93 (2-[N-(2-Hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor, Is a Direct Extracellular Blocker of Voltage-Gated Potassium Channels J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 292 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, X. Zhang, H. Kubo, D. M. Harris, G. D. Mills, J. Moyer, R. Berretta, S. T. Potts, J. D. Marsh, and S. R. Houser Ca2+ Influx-Induced Sarcoplasmic Reticulum Ca2+ Overload Causes Mitochondrial-Dependent Apoptosis in Ventricular Myocytes Circ. Res., November 11, 2005; 97(10): 1009 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Sergeant, S. Ohya, J. A. Reihill, B. A. Perrino, G. C. Amberg, Y. Imaizumi, B. Horowitz, K. M. Sanders, and S. D. Koh Regulation of Kv4.3 currents by Ca2+/calmodulin-dependent protein kinase II Am J Physiol Cell Physiol, February 1, 2005; 288(2): C304 - C313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Trailovic, A. P. Robertson, C. L. Clark, and R. J. Martin Levamisole receptor phosphorylation: effects of kinase antagonists on membrane potential responses in Ascaris suum suggest that CaM kinase and tyrosine kinase regulate sensitivity to levamisole J. Exp. Biol., December 15, 2002; 205(24): 3979 - 3988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Smyth, A. L. Abbott, B. Lee, I. Sienaert, N. N. Kasri, H. De Smedt, T. Ducibella, L. Missiaen, J. B. Parys, and R. A. Fissore Inhibition of the Inositol Trisphosphate Receptor of Mouse Eggs and A7r5 Cells by KN-93 via a Mechanism Unrelated to Ca2+/Calmodulin-dependent Protein Kinase II Antagonism J. Biol. Chem., September 13, 2002; 277(38): 35061 - 35070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A Greenwood, J. Ledoux, and N. Leblanc Differential regulation of Ca2+-activated Cl- currents in rabbit arterial and portal vein smooth muscle cells by Ca2+-calmodulin-dependent kinase J. Physiol., July 15, 2001; 534(2): 395 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. D. Kong, S. D. Koh, O. Bayguinov, and K. M Sanders Small conductance Ca2+-activated K+ channels are regulated by Ca2+-calmodulin-dependent protein kinase II in murine colonic myocytes J. Physiol., April 15, 2000; 524(2): 331 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nishimura and T. Tanaka Calcium-dependent Activation of Nuclear Factor Regulated by Interleukin 3/Adenovirus E4 Promoter-binding Protein Gene Expression by Calcineurin/Nuclear Factor of Activated T Cells and Calcium/Calmodulin-dependent Protein Kinase Signaling J. Biol. Chem., June 1, 2001; 276(23): 19921 - 19928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Corcoran and A. R. Means Defining Ca2+/Calmodulin-dependent Protein Kinase Cascades in Transcriptional Regulation J. Biol. Chem., January 26, 2001; 276(5): 2975 - 2978. [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
