Early exposure to sevoflurane inhibits Ca(2+) channels activity in hippocampal CA1 pyramidal neurons of developing
1School of Biomedical Engineering, Tianjin Medical University, Tianjin 300070, China; Laboratory of Neurobiology in Medicine, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
Insights
Early sevoflurane exposure, a common anesthetic, can inhibit voltage-gated calcium channels (VGCCs) in developing rat brains. While effects persist, recovery is observed by juvenile age.
Area of Science:
- Neuroscience
- Anesthesiology
- Developmental Biology
Background:
- Sevoflurane is a widely used inhalation anesthetic in pediatric anesthesia.
- Voltage-gated calcium channels (VGCCs) are critical for neuronal development and excitability.
- The impact of sevoflurane on developing brain VGCCs remains poorly understood.
Purpose of the Study:
- To investigate the effects of sevoflurane on VGCCs in hippocampal CA1 pyramidal neurons during rapid brain development.
- To compare the effects of different sevoflurane concentrations (2.1% and 3%) on VGCCs.
Main Methods:
- Whole-cell patch-clamp technique was employed on Sprague-Dawley rats aged 1 week.
- Rats were exposed to 2.1% or 3% sevoflurane for 6 hours.
- Calcium channel current density, activation, and inactivation curves were analyzed at various ages (1-5 weeks).
Main Results:
- Sevoflurane exposure significantly decreased Ca(2+) channel current density at weeks 1 and 2.
- 3% sevoflurane caused a rightward shift in activation and inactivation curves, indicating altered channel gating.
- The inhibitory effects were concentration-dependent, with 3% sevoflurane showing a greater impact than 2.1%.
Conclusions:
- Early sevoflurane exposure persistently inhibits VGCC activity in developing rat hippocampus.
- The observed inhibition shows recovery to normal levels by the juvenile stage.
- These findings highlight potential neurodevelopmental concerns associated with sevoflurane anesthesia in infants.
Abstract:
Sevoflurane is one of inhalation anesthetics and has been commonly used in obstetric and pediatric anesthesia. The widespread use of sevoflurane in newborns and infants has made its safety a health issue of concern. Voltage-gated Ca(2+) channels (VGCCs) play an important role in neuronal excitability and are essential for normal brain development. However, the role of sevoflurane on regulating Ca(2+) channels during the period of rapid brain development is still not well understood. The aim of this study is to explore the effects of sevoflurane on voltage-gated Ca(2+) channels for hippocampal CA1 pyramidal neurons during the period of rapid brain development. 1-week-old Sprague-Dawley rats were randomly divided into 3 groups: control group, 2.1% sevoflurane group (exposed to 2.1% sevoflurane for 6h) and 3% sevoflurane group (exposed to 3% sevoflurane for 6h). Whole-cell patch clamp technique was used. I-V curve, steady-state activation and inactivation curves of Ca(2+) channels were studied in rats of the both 3 treated groups at 5 different ages (1 week, 2 weeks, 3 weeks, 4 and 5 weeks old). After anesthesia with sevoflurane at 1-week-old rats, Ca(2+) channels current density was significantly decreased at week 1 and week 2 (p<0.01). And 3% sevoflurane exposure resulted in a rightward shift in steady-state activation curve at week 1 and week 2, as well as the inactivation curve from week 1 to week 3. However, the 2.1% sevoflurane-induced rightward shift was only found in steady-state inactivation curve of Ca(2+) channels at week 1 and week 2. Both the slope factor (k) of Ca(2+) channels activation and inactivation curves increased by 3% sevoflurane at week 1 (p<0.05). Therefore, early exposure to sevoflurane persistently inhibits Ca(2+) channels activity in hippocampal CA1 pyramidal neurons of developing rats but the development of Ca(2+) channels recovers to normal level at juvenile age. Moreover, the inhibition of 3% sevoflurane on VGCCs is greater than that of 2.1% sevoflurane.
