NE对脊髓运动神经元外周传入突触传递及其表观受体动力学的影响

Effects of NE on afferent synaptic transmission and its apparent receptor kinetics of spinal cord motoneurons

目的:探讨去甲肾上腺素(NE)对新生大鼠离体脊髓运动神经元(MN)外周传入所诱发的兴奋性突触后电位(EPSP)及其表观受体动力学的影响。方法:应用新生(8~14 d)SD大鼠脊髓横切片(400~500μm)MN细胞内记录技术,观察NE对MN细胞电生理特性及同侧背根(iDR)电刺激诱发的兴奋性突触后电位(iDR-EPSP)的影响,并通过表观受体动力学方法分析iDR-EPSPs的受体动力学。结果:在7个稳定记录的MN,累积灌流1、5和25μmol/L的NE各15 min,不仅均浓度依赖性诱导去极化反应,增大膜电阻和升高动作电位发放频率(I-F曲线上移)(均P<0.01),还降低iDR-EPSP幅度、曲线下面积、时程和衰减时间(P<0.05);在5μmol/L NE抑制iDR-EPSP的10个MN,其iDR-EPSPs的表观受体动力学分析显示,NE降低表观最大反应(V max)和表观结合速率常数(K 1)(均P<0.05),而增加表观平衡解离常数(K T)(P<0.05),及表观解离速率常数(K 2)可能存在增大趋势(P>0.05)。结论:在NE通过兴奋MN而抑制外周传入兴奋性突触传递的调控中可能涉及降低突触后受体亲和力的机制。

Objective:To investigate the effects of norepinephrine on excitatory postsynaptic potential(EPSP)and its apparent receptor kinetics evoked by afferents in neonatal rat spinal cord motoneurons(MNs)in vitro.Methods:The EPSPs induced by electrical stimulation of ipsilateral dorsal root(iDR,iDR-EPSP)were recorded using intracellular recording technique of MNs in the spinal cord transverse slices(400-500μm)prepared from neonatal(8-14 d)SD rats.NE-induced changes of iDR-EPSP and electrophysiological characteristic were observed,and receptor kinetics of iDR-EPSPs was analyzed by the apparent receptor kinetics method.Results:In the 7 stably recorded MNs with iDR-EPSP,perfusion in turn with 1,5 and 25μmol/L NE for 15 min each not only concentration-dependently induced depolarization with increasing membrane resistance and action potential firing frequency(I-F curve shifted up)(both P<0.01),but also decreased the EPSP amplitude,area under curve(AUC),duration and decay time(both P<0.05);In 10 MNs with inhibited iDR-EPSP after bath of 5μmol/L NE,the apparent receptor kinetic analyses of iDR-EPSPs showed that NE decreased the apparent maximum response(V max)and the apparent association rate constant(K 1)(both P<0.05),while increased the apparent equilibrium dissociation constant(K T)(P<0.05)and tended to increase the apparent dissociation rate constant(K 2)(P>0.05).Conclusion:The mechanism underlying NE modulation of MNs by exciting MN while inhibiting afferent excitatory synaptic transmission may involve a decrease in postsynaptic receptor affinity.