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

By Manabu Kubokawa, Kazuyoshi Nakamura and You Komagiri


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

Topics: Review Article
Publisher: SAGE-Hindawi Access to Research
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