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Propofol and ketamine-induced anesthetic depth-dependent decrease of CaMKII phosphorylation levels in rat hippocampus
1Department of Anesthesiology, Capital Medical University Affiliated Beijing Tongren Hospital, Beijing, China.
Abstract:
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.
Insights
Propofol and ketamine decrease CaMKII phosphorylation in rats, impacting brain function during anesthesia. This effect is dependent on anesthetic depth and drug dosage, with levels returning to normal after 240 minutes.
Area of Science:
- Neuroscience
- Anesthesiology
- Molecular Biology
Background:
- Ca/calmodulin-dependent protein kinase II (CaMKII) activation via autophosphorylation at threonine 286 is crucial for neuronal excitability and neurotransmission.
- Propofol and ketamine, common anesthetics, influence intracellular calcium levels through NMDA receptors or voltage-dependent calcium channels, but with distinct mechanisms.
Purpose of the Study:
- To investigate the effects of propofol and ketamine on CaMKII total protein and phosphorylated CaMKII (p-CaMKII) levels in rat brains.
- To determine if these effects are dependent on anesthetic depth, drug dosage, and brain region.
Main Methods:
- Rats were administered varying doses of propofol and ketamine via intraperitoneal injection.
- Brain tissue (hippocampus and frontal cortex) was analyzed for CaMKII total protein and p-CaMKII levels at different time points (5, 30, 60, 240 minutes) post-injection.
- Immunostaining was used to confirm p-CaMKII depression in specific brain regions.
Main Results:
- Both propofol and ketamine reduced p-CaMKII levels in a manner dependent on anesthetic depth, without affecting total CaMKII protein.
- Ketamine exhibited a dose-dependent depression of p-CaMKII (50, 100, 150 mg/kg).
- p-CaMKII levels decreased significantly starting at 5 minutes post-propofol (100 mg/kg) and at 30 minutes post-ketamine (100 mg/kg) in the hippocampus, with frontal cortex showing effects at 5 minutes for both drugs.
Conclusions:
- Decreased p-CaMKII levels correlate with anesthetic depth achieved by propofol and ketamine.
- These findings suggest a potential mechanism linking propofol and ketamine's effects on central nervous system function and their clinical anesthetic properties to alterations in CaMKII phosphorylation.
