Research ReportEarly exposure to sevoflurane inhibits Ca2+ channels activity in hippocampal CA1 pyramidal neurons of developing rats

- Properties of VGCCs in rat hippocampal neurons during development were studied.
- Effects of sevoflurane on VGCCs during development were assessed.
- Sevoflurane inhibits VGCCs activity of hippocampal CA1 neurons.
- The inhibition of 3% sevoflurane on VGCCs is greater than that of 2.1% sevoflurane.

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 Ca2+ channels (VGCCs) play an important role in neuronal excitability and are essential for normal brain development. However, the role of sevoflurane on regulating Ca2+ 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 Ca2+ 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 6 h) and 3% sevoflurane group (exposed to 3% sevoflurane for 6 h). Whole-cell patch clamp technique was used. I-V curve, steady-state activation and inactivation curves of Ca2+ 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, Ca2+ 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 Ca2+ channels at week 1 and week 2. Both the slope factor (k) of Ca2+ channels activation and inactivation curves increased by 3% sevoflurane at week 1 (p<0.05).Therefore, early exposure to sevoflurane persistently inhibits Ca2+ channels activity in hippocampal CA1 pyramidal neurons of developing rats but the development of Ca2+ channels recovers to normal level at juvenile age. Moreover, the inhibition of 3% sevoflurane on VGCCs is greater than that of 2.1% sevoflurane.