Friederich P, Urban B W
Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universität Bonn.
Anaesthesist. 1997 May;46(5):434-6. doi: 10.1007/s001010050422.
There is no data available on the action of etomidate on ion currents in human neuronal cells. Therefore the effects of etomidate on a human neuronal delayed rectifier potassium current were investigated.
Outward rectifying potassium currents of human neuroblastoma SH-SY5Y cells were measured using the whole cell patch-clamp technique. Cells were grown in RPMI-medium (+Pen/Strep and FCS) at 37 degrees C and 5% CO2. The holding potential was -80 mV. Potassium currents were evoked by depolarizing the membrane potential to values from -50 mV to +90 mV in 10 mV steps using an EPC-7 patch-clamp amplifier (List medical electronics) and pclamp version 5.71 (Axon instruments).
Etomidate differentially inhibited steady-state and peak potassium current with IC50-values of 170 microM for peak current suppression and 120 microM for steady-state current respectively. Etomidate induced inactivation-like behaviour of the potassium current and changed the voltage dependence of potassium current activation.
The results demonstrate that etomidate has more than one effect on the potassium current, indicating the complexity of general anaesthetic actions on neuronal targets. The actions of etomidate on human neuronal potassium currents may potentially contribute to the myocloni observed with this general anaesthetic agent during induction of anaesthesia.
关于依托咪酯对人神经细胞离子电流的作用尚无可用数据。因此,研究了依托咪酯对人神经细胞延迟整流钾电流的影响。
采用全细胞膜片钳技术测量人神经母细胞瘤SH-SY5Y细胞的外向整流钾电流。细胞在含有青霉素/链霉素和胎牛血清的RPMI培养基中于37℃和5%二氧化碳条件下培养。钳制电位为-80mV。使用EPC-7膜片钳放大器(List医疗电子公司)和pclamp 5.71版本(Axon仪器公司),以10mV步长将膜电位从-50mV去极化至+90mV来诱发钾电流。
依托咪酯分别以170μM和120μM的IC50值差异性抑制稳态和峰值钾电流,对峰值电流抑制的IC50值为170μM,对稳态电流抑制的IC50值为120μM。依托咪酯诱导钾电流出现失活样行为,并改变钾电流激活的电压依赖性。
结果表明依托咪酯对钾电流有多种作用,提示全身麻醉药对神经靶点作用的复杂性。依托咪酯对人神经钾电流的作用可能是该全身麻醉药在麻醉诱导期间出现肌阵挛的潜在原因。