Dynamic regulation of the activated, autophosphorylated state of Ca2+/calmodulin-dependent protein kinase II by acute neuronal excitation in vivo.
Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated in various neuronal functions, including synaptic plasticity. To examine the physiological regulation of its activated, autophosphorylated state in relation to acute neuronal excitation in vivo, we studied the effect of electroconvulsive treatment in rats on CaMKII activity and in situ autophosphorylation levels. As early as 30 s after the electrical stimulation, a profound but transient decrease in its Ca2+/calmodulin-independent activity, as well as in the level of its autophosphorylation at Thr286(alpha)/Thr287(beta) measured by using phosphorylation state-specific antibodies, was observed in homogenate from hippocampus and parietal cortex, which was reversible in 5 min. In the later time course, a moderate, reversible increase, which peaked at around 60 min after the electrical stimulation, was observed in parietal cortex but not in hippocampus. The early-phase decrease was found to occur exclusively in the soluble fraction. In addition, partial translocation of CaMKII from the soluble to the particulate fraction seems to have occurred in this early phase. Thus, the activated, autophosphorylated state of CaMKII is under dynamic and precise regulation in vivo, and its regulatory mechanisms seem to have regional specificity.
Yamagata
Y
Y
Laboratory of Neurochemistry, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan.
Obata
K
K
D000818:Animals; D000918:Antibody Specificity; D000927:Anticonvulsants / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology / Q000503:physiopathology; D015151:Immunoblotting; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D009474:Neurons / Q000201:enzymology*; D010296:Parietal Lobe / Q000201:enzymology / Q000503:physiopathology; D010634:Phenobarbital / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology
D000927:Anticonvulsants; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003975:Diazepam; D010634:Phenobarbital