1 Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai 200040, China

2 Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital, College of Medicine, Korea University, Seoul 08308, Korea

3 Department of Anesthesiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China

4 Department of Physiology and Neuroscience Research Institute, College of Medicine, Korea University, Seoul 02841, Korea

5 Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China

Abstract 

In the current study, we sought to investigate whether T-type Ca2+ channels (TCCs) in the brain are involved in generating post-anesthetic hyperexcitatory behaviors (PAHBs). We found that younger rat pups (postnatal days 9–11) had a higher incidence of PAHBs and higher PAHB scores than older pups (postnatal days 16–18) during emergence from sevoflurane anesthesia. The power spectrum of the theta oscillations (4 Hz–8 Hz) in the prefrontal cortex was significantly enhanced in younger pups when PAHBs occurred, while there were no significant changes in older pups. Both the power of theta oscillations and the level of PAHBs were significantly reduced by the administration of TCC inhibitors. Moreover, the sensitivity of TCCs in the medial dorsal thalamic nucleus to sevoflurane was found to increase with age by investigating the kinetic properties of TCCs in vitro. TCCs were activated by potentiated GABAergic depolarization with a sub-anesthetic dose of sevoflurane (1%). These data suggest that (1) TCCs in the brain contribute to the generation of PAHBs and the concomitant electroencephalographic changes; (2) the stronger inhibitory effect of sevoflurane contributes to the lack of PAHBs in older rats; and (3) the contribution of TCCs to PAHBs is not mediated by a direct effect of sevoflurane on TCCs.

Keywords

Emergence agitation; Neonatal rat; General anesthesia; Sevoflurane; T-type calcium channel; Theta wave

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