Background: Although protein kinase C-γ (PKC-γ) is a target for the effects of volatile anesthetics, the molecular mechanisms of the kinase function remain unclear. We examined the effects of different types of anesthetics on PKC-γ knockout mice, and investigated the dynamics of the kinase in mouse brain.
Methods: We measured the required number of times for loss of righting reflex (rtfLORR) after administration of isoflurane, sevoflurane, and propofol on PKC-γ knockout mice and compared 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 of wild-type mice anesthetized by these anesthetics.
Results: Isoflurane and sevoflurane significantly prolonged the rtfLORRs in PKC-γ knockout mice compared with those in wild-type mice, while no significant difference was observed between knockout and wild-type mice treated with propofol. Examination of the cellular fractions showed that PKC-γ was significantly decreased, whereas p-PKC-γ was significantly increased in the synaptic membrane fraction (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.