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Published on: August 14, 2015
Role of T-type Calcium Channels in Generating Hyperexcitatory Behaviors during Emergence from Sevoflurane Anesthesia
Feng-Yan Shen1, Byung-Gun Lim2, Wen Wen3
1Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Insights
T-type calcium channels (TCCs) in the brain contribute to post-anesthetic hyperexcitatory behaviors (PAHBs) in young rats. Inhibiting TCCs reduced both PAHBs and brain wave changes, suggesting a key role for these channels.
Area of Science:
- Neuroscience
- Anesthesiology
- Developmental Biology
Background:
- Post-anesthetic hyperexcitatory behaviors (PAHBs) are observed during emergence from anesthesia.
- The role of specific ion channels, such as T-type Ca2+ channels (TCCs), in PAHBs is not fully understood.
- Age-dependent differences in anesthetic effects and behavioral responses are well-documented.
Purpose of the Study:
- To investigate the involvement of brain T-type Ca2+ channels (TCCs) in the generation of post-anesthetic hyperexcitatory behaviors (PAHBs).
- To explore the age-related changes in TCC sensitivity and their contribution to PAHBs during sevoflurane anesthesia emergence.
Main Methods:
- Comparison of PAHBs incidence and severity between younger (postnatal days 9-11) and older (postnatal days 16-18) rat pups during sevoflurane emergence.
- Analysis of electroencephalographic theta oscillations (4 Hz-8 Hz) in the prefrontal cortex.
- Administration of TCC inhibitors and assessment of their effects on PAHBs and theta oscillations.
- In vitro investigation of TCC kinetic properties and sensitivity to sevoflurane in the medial dorsal thalamic nucleus.
Main Results:
- Younger rat pups exhibited a higher incidence and severity of PAHBs compared to older pups.
- Enhanced theta oscillation power in the prefrontal cortex was observed in younger pups during PAHBs.
- TCC inhibition significantly reduced both theta oscillation power and PAHBs.
- In vitro studies showed increased TCC sensitivity to sevoflurane with age.
- TCCs were activated by potentiated GABAergic depolarization under sub-anesthetic sevoflurane (1%).
Conclusions:
- Brain T-type Ca2+ channels (TCCs) play a significant role in generating PAHBs and associated electroencephalographic changes.
- The reduced incidence of PAHBs in older rats may be attributed to a stronger inhibitory effect of sevoflurane, potentially related to age-dependent TCC modulation.
- The contribution of TCCs to PAHBs is not directly mediated by sevoflurane acting on the channels themselves.
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.
