【摘要】 目的探讨芬太尼对大鼠海马锥体神经元GABAA受体的作用。方法采用酶-机械法急性分离出生3-10 d SD大鼠的海马锥体神经元,用全细胞膜片钳技术记录锥体神经元GABAA受体介导的Cl-电流(GABA电流,IGABA),不同浓度的GABA和1 μmol/L GABAA受体特异性拮抗剂荷包牡丹碱诱发并确定IGABA;用不同浓度的芬太尼和1．0 μmol/L μ受体特异性拮抗剂CTAP评价芬太尼对30 μmol/L GABA诱发IGABA的影响。结果 GABA诱发内向电流(IGABA),其EC50为23．73μmol/L,荷包牡丹碱阻断IGABA;芬太尼剂量依赖性地抑制IGABA,其EC50为0．011 μmol/L,并缩短IGABA的脱敏感时间常数τdes;CTAP使芬太尼抑制GABA诱发IGABA的EC50升至0．414μmol/L;芬太尼不改变IGABA的翻转电位 ECl-(-3．0mV)。结论芬太尼可抑制大鼠海马锥体神经元GABAA受体的功能。更多还原

【Abstract】 Objective To investigate the inhibitory effects of fentanyl on GABAA receptors in hippocampal pyramidal neurons of rat.Methods Pyramidal neurons were acutely isolated from 3-10 day old SD rats of either sex by enzymatic-mechanic method. GABAA receptor mediated currents ( IGABA) were recorded using voltage clamped whole cell patch clamp technique in gap-free mode at the holding potential (VH) of - 50 mV. Current-voltage relationship of IGABA was obtained in ramp protocol ranging from + 30 mV to - 110 mV and lasting for 1 600 ms. Data were collected by using a system consisting of Axopatch 200B patch-clamp amplifier, Pentium Ⅲ computer and Digidata 1200 interface. All experiments were performed at room temperature (22-25℃). Five to twelve neurons were used for each fentanyl concentration. The effects of fentanyl from 1.0 × 10-5 μmol·L-1 to 10. 0 μmol·L-1 were evaluated by the inhibition rate of the peak amplitude of IGABA, the desensitization time constant (τdes) of IGABA and the reversal potential (Ecl- ) of IGABA. A μ-opioid receptor selective antagonist CTAP 1 μmol·L-1 was applied and its effects on fentanyl were recorded. Results (1) GAB A 1-1 000 μmol·L-1 induced inward currents (IGABA) dose-dependently with an EC50 of 23.73 μmol·L-1.IGABA induced by GABA 30 μmol·L-1 was blocked by bicuculline 1 μmol·L-1. (2) Fentanyl depressed IGABA dose-dependently with EC50 of 0.011 μmol·L-1 and shortened the rdes of IGABA.(3) The inhibitory effects of fentanyl on IGABA were antagonized by CTAP. (4) Fentanyl 0.01 μmol·L-1 and CTAP did not influence the reversal potential of IGABA (Ecl- -3.0 mV) .Conclusion Fentanyl inhibits the function of GABAA receptors through μ-opioid receptors in hippocampal pyramidal neurons. Hippocampus may play a role in the neuroexcitatory effects of opioids.更多还原