褪黑激素对新生大鼠海马神经元延迟整流钾电流的影响

目的 用膜片钳技术观察褪黑激素对电压门控性延迟整流钾电流(Ik)的影响,探讨褪黑激素在中枢神经系统的作用机制及其生物学意义.方法 选择7～12 d原代培养的新生Wistar大鼠海马锥体神经元,用膜片钳电压钳全细胞记录模式观察Ik的基本电生理特点,并观察不同浓度褪黑激素,包括1、10、100 nmol/L、1、10、100 μmol/L和1 mmol/L对Ik的幅度及动力学特性的影响.结果 利用海马锥体神经元的钾电流对4-AP、TEA的敏感性及电生理特性的不同可分离出激活、失活缓慢,具有强烈外向整流特性的延迟整流钾电流.褪黑激素对海马锥体神经元Ik的影响是快速、可逆、呈电压依赖性的,但对其激活曲线没有影响.褪黑激素对Ik的作用具有浓度依赖性.1～100nmoI/L的褪黑激素可逐渐递增地增加Ik幅度;1～100 μmol/L褪黑激素对Ik的增加程度随浓度增加而增大,而1 mmol/L褪黑激素的增加程度却减小.结论 褪黑激素可逆地增强体外培养新生大鼠海马神经元的Ik电流,这或许参与了神经元损伤和记忆损害的某些环节.

Effects of melatonin on the voltage-gated delayed rectifier potassium channels of cultured hippocampal neurons of new-born rats

OBJECTIVE: To investigate the effects of melatonin on voltage-gated delayed rectifier potassium channels. METHODS: Hippocampus neurons were obtained from newborn Wistar rat and cultured. Primary cultured for 7 to 12 days of new-born Wistar rat were selected as objectives. Patch clamp whole-cell recording technique was used on the hippocampus neurons cultured for 7 to 12 day. to record the delayed rectifier potassium current to analyze the basic electrophysiological characteristics. The effects of melatonin of the concentrations of 1 nmol/L, 10 nmol/L, 100 nmol/L, 1 mol/L, 10 mol/L, 100 mol/L, and 1 mmol/L on the amplitudes and kinetics of delayed rectifier potassium currents were investigated. RESULTS: With different voltage protocols and specific blockers of potassium channel (4-AP and TEA) a delayed rectifier potassium current that activated and inactivated slowly and had the outward rectifying characteristics (Ik) from the outward potassium currents in cultured new-born hippocampus neurons was separated. The effect of melatonin on the delayed rectifier channel was rapid, reversible and voltage-dependent Melatonin had no effect on the kinetic characteristics of the I -V curve. Melatonin increased the potassium current concentration-dependently. 1 - 100 nmol/L melatonin increased the amplitude of potassium current gradually; the effects of 1 - 100 micromol/L melatonin on the potassium current increased concentration-dependently, while the action of 1 mmol/L melatonin decreased. CONCLUSION: Melatonin reversibly increases the rectifier delayed potassium currents of the cultured hippocampus neurons of new-born rat. This may be involved in some aspects of physiological and pathological significance of potassium currents.