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

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 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 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 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.