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Enzyme Research
Volume 2011 (2011), Article ID 587359, 5 pages
Review Article

Interaction between Calcineurin and Ca2+/Calmodulin Kinase-II in Modulating Cellular Functions

Department of Physiology, Iwate Medical University School of Medicine, 2-1-1 Nishitokuda, Yahaba, Iwate 028-3694, Japan

Received 1 February 2011; Accepted 1 April 2011

Academic Editor: Heung Chin Cheng

Copyright © 2011 Manabu Kubokawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Roles of calcineurin (CaN), a Ca2+/calmodulin- (CaM-) dependent protein phosphatase, and Ca2+/CaM-dependent protein kinase-II (CaMKII) in modulating K+ channel activity and the intracellular Ca2+ concentration ([Ca2+]i) have been investigated in renal tubule epithelial cells. The channel current through the cell membrane was recorded with the patch-clamp technique, and [Ca2+]i was monitored using fura-2 imaging. We found that a CaN-inhibitor, cyclosporin A (CyA), lowered the K+ channel activity and elevated [Ca2+]i, suggesting that CyA closes K+ channels and opens Ca2+-release channels of the cytosolic Ca2+-store. Moreover, both of these responses were blocked by KN-62, an inhibitor of CaMKII. It is suggested that the CyA-mediated response results from the activation of CaMKII. Indeed, Western blot analysis revealed that CyA increased phospho-CaMKII, an active form of CaMKII. These findings suggest that CaN-dependent dephosphorylation inhibits CaMKII-mediated phosphorylation, and the inhibition of CaN increases phospho-CaMKII, which results in the stimulation of CaMKII-dependent cellular actions.