Activation of Ca2+/calmodulin-dependent protein kinase IV in cultured rat hippocampal neurons

Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV) is a multifunct ional enzyme that is abundantly present in the nuclei of neurons. We report the properties of phosphorylation and activation of CaM kinase IV in compa rison to CaM kinase II in cultured rat hippocampal neurons. Phosphorylation and activity of CaM kinase IV as well as CaM kinase II were increased by t reatment of neurons either with glutamate or high K+, Glutamate-induced pho sphorylation and activity of CaM kinase IV were blocked by N-methyl-D-aspar ate (NMDA) antagonists, and NMDA application instead of glutamate did incre ase CaM kinase IV phosphorylation. CaM kinase IV phosphorylation was also i ncreased by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), an d was blocked by an inhibitor of NMDA receptor. The AM PA-induced phosphory lation was blocked by tetrodotoxin, a Na+ channel blocker, that was expecte d to block endogenous glutamate transmission indirectly. On the other hand, high K+-induced phosphorylation and activation were not blocked by inhibit ors of glutamate receptors, and effectively blocked by nifedipine, an L-typ e Ca2+ channel blocker. These properties were similar between CaM kinase IV and CaM kinase II. J. Neurosci, Res. 59:594-600, 2000. (C) 2000 Wiley-Liss , Inc.