大鼠海马锥体神经元延迟整流钾电流的发育变化

Changes of the delayed rectifier potassium currents in rat hippocampal pyramidal neurons during the period of postnatal development

目的研究大鼠海马锥体细胞延迟整流钾电流(IK)在出生后不同发育阶段的变化。方法采用膜片钳全细胞记录模式比较3个不同年龄组,即出生后7～10天(P7-10组)、25～30天(P25-30组)和56～60天(P56-60组)Wistar大鼠急性分离的海马锥体神经元IK的变化及通道动力学和药理学特征。结果随着动物的发育,IK的电流密度上调,由P7-10的(32±13)pA/pF逐渐增加到P25-30的(64±20)pA/pF和P56-60的(70±18)pA/pF。随年龄增大,IK的激活曲线左移,其半数最大激活电位(V1/2)由-12.2mV逐渐增加到-17.8mV,而斜率因子无明显变化。四乙铵(TEA)可剂量依赖性地抑制IK,其中P7-10组的IK对低浓度的TEA(2和5mmol/L)较P25-30及P56-60组更敏感。结论在大鼠海马锥体神经元的发育过程中IK逐渐增加,并伴有通道激活动力学和药理学特性的改变。上述变化可能与海马锥体神经元的成熟以及认知功能的日益完善有关。

Objective To study the developmental properties of delayed rectifier potassium currents （ IK ） in maturing hippocampal pyramidal neurons. Methods Whole cell configuration of the patch - clamp techniques were used to define the characters of IK in the maturing hippocampal pyramidal neurons acutely isolated from Wistar rasts of three postnatal age groups： P7-10, P25-30 and P56-60. Results With the postnatal age increasing, the expression of IK was upregu- lated from 32 pA/pF in P7-10 group to 64 pA/pF in P25 -30 and 70 pA/pF in P56-60 group. The steady - state activation curves of IK in hippocampal pyramidal neurons showed a left shift and the half - activation potentials （ V1/2 ） changed from - 12.2 mV （slope factor k = 13.8） in P7-10 group to - 16.7 mV （ k = 14.0） and - 17.8 mV （ k = 13.7） in P25 -30 and P56-60 groups respectively. TEA could reduce IK in a dose- dependent manner. IK of P7-10 was found more sensitive to 2 mmol/L and 5 mmol/L TEA than that of P25 -30 and P56-60. Conclusion These results indicate that the current density of IK increases with the postnatal development, which may be related to the maturation of hippocampal neurons and the progress of human cognition.