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Published on: March 18, 2022
Effects of different types of anesthetic agents on cellular protein kinase C-γ dynamics in mouse brain
Akiko Takeda1, Ryoichi Miyashita, Takeo Nagura
1Department of Anesthesiology, Tokyo Medical University Hospital, Tokyo, Japan. a-takeda @ tokyo-med.ac.jp
Background/Aims:
Although protein kinase C-γ (PKC-γ) is a target for the effects of volatile anesthetics, the molecular mechanisms of the kinase function during their action remain unclear. We examined the effects of different types of anesthetics on PKC-γ knockout mice. Furthermore, we investigated the dynamics of the kinase in brain cells obtained from mice anesthetized with these anesthetics.
Methods:
We measured the required times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, or propofol on PKC-γ knockout mice and compared the times with those of wild-type mice. We also used immunoblotting to investigate the intracellular distribution of PKC-γ and phosphorylated PKC-γ (p-PKC-γ) in brain cell fractions obtained from wild-type mice during the loss of righting reflex induced by these anesthetics.
Results:
Isoflurane (2.6%) and sevoflurane (3.4%) used at twice the minimum alveolar concentration significantly prolonged the rtfLORRs in PKC-γ knockout mice compared to those in wild-type mice. On the other hand, no significant difference was observed between knockout and wild-type mice treated with propofol (200 mg/kg). Examination of the cellular fractions isolated from volatile anesthetic-treated mouse brains showed that PKC-γ was significantly decreased in the synaptic membrane fraction (P2), whereas p-PKC-γ was significantly increased in P2. There was no significant change in the supernatant fraction (S). In propofol-treated mice, PKC-γ and p-PKC-γ showed no significant changes in P2 or S.
Conclusion:
Our results provide new evidence to support the possibility of the involvement of PKC-γ in the actions of volatile anesthetics.
Insights
Volatile anesthetics like isoflurane and sevoflurane affect protein kinase C-gamma (PKC-γ) in mouse brains, altering its synaptic distribution. Propofol did not show these effects, suggesting PKC-γ is involved in volatile anesthetic action.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Protein kinase C-gamma (PKC-γ) is implicated in volatile anesthetic effects.
- The precise molecular mechanisms of PKC-γ in anesthesia are not fully understood.
Purpose of the Study:
- To investigate the role of PKC-γ in the action of different anesthetics.
- To examine anesthetic-induced changes in PKC-γ dynamics within brain cells.
Main Methods:
- Compared loss of righting reflex times in PKC-γ knockout and wild-type mice treated with isoflurane, sevoflurane, or propofol.
- Utilized immunoblotting to analyze PKC-γ and phosphorylated PKC-γ (p-PKC-γ) distribution in brain cell fractions.
Main Results:
- Isoflurane and sevoflurane significantly prolonged anesthetic recovery in PKC-γ knockout mice.
- Propofol did not alter recovery times between knockout and wild-type mice.
- Volatile anesthetics decreased synaptic PKC-γ and increased synaptic p-PKC-γ, with no changes observed after propofol.
Conclusions:
- Results suggest PKC-γ is involved in the mechanism of action of volatile anesthetics.
- PKC-γ's altered synaptic localization and phosphorylation state may mediate volatile anesthetic effects.
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