Propofol and ketamine-induced anesthetic depth-dependent decrease of CaMKII phosphorylation levels in rat hippocampus and cortex.
Ca/calmodulin-dependent protein kinase II (CaMKII) activation through autophosphorylation at threonine 286 was involved in the modulation of neuronal excitability and neurotransmission. Both propofol and ketamine may affect the intracellular Ca levels through N-methyl-D-aspartate receptors or voltage-dependent Ca channels, but they have different mechanisms in general anesthesia. The purpose of this study was to investigate the effects of propofol and ketamine on CaMKII total protein and phosphorylation (p-CaMKII) levels in the brain of rats. We found that both propofol and ketamine could induce a decrease of p-CaMKII, not CaMKII total protein, in an anesthetic depth-dependent manner, whereas only ketamine caused a dose (50, 100, and 150 mg/kg)-dependent depression of p-CaMKII in hippocampus and frontal cortex of rats after intraperitoneal injections for 30 minutes. The significant depressions of p-CaMKII started at 5 minutes both in hippocampus and frontal cortex of rats after 100 mg/kg propofol treatment, whereas 100 mg/kg ketamine-induced significant depression of p-CaMKII initiated at 30 minutes in hippocampus and 5 minutes (no reduction observed at 15 min) in frontal cortex of rats. The maximum reduction of p-CaMKII with both drugs was at 60 minutes, and then restored to control level at 240 minutes. In addition, we confirmed the depression of p-CaMKII in hippocampus and frontal cortex of rats after 100 mg/kg of propofol or ketamine treatment for 60 minutes by using immunostaining. These results suggested that decreased p-CaMKII levels correlate with anesthetic depths achieved by propofol and ketamine, which may be related to the effects of propofol and ketamine on central nervous system function and their clinical effect.
Cui
Xu
X
Department of Anesthesiology, Capital Medical University Affiliated Beijing Tongren Hospital, Beijing, China.
Li
Junfa
J
Li
Tianzuo
T
Ji
Fang
F
Bu
Xiangning
X
Zhang
Nan
N
Zhang
Bingxi
B
D000758:Anesthesia; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007150:Immunohistochemistry; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D007649:Ketamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D015742:Propofol