title: Early exposure to sevoflurane inhibits Ca(2+) 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 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.
authors: School 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. Electronic address: liuzitong.aili@163.com.
authors: Aili
authors: A
authors: Liu
authors: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300070, China; Tianjin Research Institute of Anesthesiology, Tianjin 300070, China. Electronic address: liyizelisa@126.com.
authors: Yize
authors: Y
authors: Li
authors: Ministry of Education Key Laboratory of Child Development and Disorders, and Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children׳s Hospital of Chongqing Medical University, Chongqing 400014, China. Electronic address: tantao_tijmu@126.com.
authors: Tao
authors: T
authors: Tan
authors: School 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; Tianjin Neurological Institute, Tianjin 300070, China. Electronic address: tianx@tijmu.edu.cn.
authors: Xin
authors: X
authors: Tian
mesh_terms: D000367:Age Factors; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000009:adverse effects*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: Activity of Ca(2+) channels; Inhibit; Sevoflurane; The period of rapid brain development