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Calcium/Calmodulin-dependent protein kinase IIdelta2 and gamma insoforms regulate potassium currents of rat brain capillary endothelial cells under hypoxic conditions

Item Type:Article
Title:Calcium/Calmodulin-dependent protein kinase IIdelta2 and gamma insoforms regulate potassium currents of rat brain capillary endothelial cells under hypoxic conditions
Creators Name:Balla, Z. and Hoch, B. and Karczewski, P. and Blasig, I.E.
Abstract:Endothelial K+ and Ca2+ homeostasis plays an important role in the regulation of tissue supply and metabolism under normal and pathological conditions. However, the exact molecular mechanism of how Ca2+ is involved in the regulation of K+ homeostasis in capillary endothelial cells, especially under oxidative stress, is not clear. To reveal Ca2+-triggered pathways, which modulate K+ homeostasis, Ca2+/calmodulin-dependent protein kinase II and voltage-gated outward K+ currents were studied in rat brain capillary endothelial cells under hypoxia. Whole cell voltage-clamp measurements showed voltage-gated outward K+ current with transient and sustained components. mRNA and protein of Ca2+/calmodulin-dependent protein kinase II {delta}2 and two {gamma} isoenzymes were identified. Activation of the isoforms (autophosphorylation) was typically achieved by the Ca2+ ionophore ionomycin, which was prevented by the Ca2+/calmodulin-dependent protein kinase II-specific inhibitor KN-93. Hypoxia resulted in autophosphorylation of the {delta}2 and {gamma}B isoforms, augmented the current amplitude, increased the inactivation time constant, and decreased the extent of inactivation of the transient current. KN-93 prevented both the activation of the isoforms and the alterations in the K+ current characteristics. It is concluded that the activation of Ca2+/calmodulin-dependent protein kinase II decreases inactivation of the voltage-gated outward K+ current, thereby counteracting depolarization of the hypoxic endothelium.
Keywords:Anoxia, Brain, Ca(2+)-Calmodulin Dependent Protein Kinase, Capillaries, Cell Line, Cultured Cells, Drug Dose-Response Relationship, Immunoblotting, Messenger RNA, Phase-Contrast Microscopy, Patch-Clamp Techniques, Potassium, Potassium Channels, Protein Binding, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Tertiary Protein Structure, Vascular Endothelium, Animals, Rats
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:277
Number:24
Page Range:21306-21314
Date:14 June 2002
Official Publication:https://doi.org/10.1074/jbc.M200553200
PubMed:View item in PubMed

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