Actions of noradrenaline on substantia gelatinosa neurones in the rat spinal cord revealed by in vivo patch recording
Actions of noradrenaline on substantia gelatinosa neurones in the rat spinal cord revealed by in vivo patch recording
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DOI：
10.1113/jphysiol.2003.054932
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发表时间：
2004-03-01
影响因子：
5.5
通讯作者：
Yoshimura, M
中科院分区：
文献类型：
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作者：
Sonohata, M;Furue, H;Yoshimura, M
为阐明脊髓去甲肾上腺素下行通路介导的抗伤害性感受机制，采用在体全细胞膜片钳技术研究了去甲肾上腺素（NA）对大鼠胶状质（SG）神经元伤害性突触反应的影响及其突触后作用。在氨基甲酸乙酯麻醉下，暴露腰髓后将大鼠固定在立体定位仪中。在电流钳模式下，捏刺激施加到同侧后肢引起了大量的EPSP，其中一些启动了动作电位。将NA灌注到脊髓表面使膜超极化（5.0-9.5 mV）并抑制动作电位。在电压钳模式下（V-H，-70 mV），NA产生一个外向电流，该电流被加入到移液管溶液中的Cs+和GDP-β-S阻断，并降低伤害性刺激诱发的EPSC的幅度。在阻断NA的突触后作用的情况下，SG神经元的诱发和自发EPSC仍被观察到减少，从而表明NA的突触前和突触后作用。NA诱导的外向电流显示出明显的剂量依赖性（EC_（50），20 μ M），翻转电位为-88 mV。外向电流被α（2）-肾上腺素受体激动剂可乐定模拟，并被α（2）-肾上腺素受体拮抗剂育亨宾抑制，但不被α（1）-和β-拮抗剂抑制。这些结果表明，NA作用于突触前部位，以减少伤害性刺激诱导的EPSC，并作用于突触后SG神经元，通过G蛋白介导的α（2）-肾上腺素能受体激活K+通道，诱导外向电流，从而产生抗伤害性效应。
To elucidate the mechanisms of antinociception mediated by the descending noradrenergic pathway in the spinal cord, the effects of noradrenaline (NA) on noxious synaptic responses of substantia gelatinosa (SG) neurones, and postsynaptic actions of NA were investigated in rats using an in vivo whole-cell patch-clamp technique. Under urethane anaesthesia, the rat was fixed in a stereotaxic apparatus after the lumbar spinal cord was exposed. In the current-clamp mode, pinch stimuli applied to the ipsilateral hindlimb elicited a barrage of EPSPs, some of which initiated an action potential. Perfusion with NA onto the surface of the spinal cord hyperpolarized the membrane (5.0-9.5 mV) and suppressed the action potentials. In the voltage-clamp mode (V-H, -70 mV), the application of NA produced an outward current that was blocked by Cs+ and GDP-beta-S added to the pipette solution and reduced the amplitude of EPSCs evoked by noxious stimuli. Under the blockade of postsynaptic actions of NA, a reduction of the evoked and spontaneous EPSCs of SG neurones was still observed, thus suggesting both pre- and postsynaptic actions of NA. The NA-induced outward currents showed a clear dose dependency (EC50, 20 muM), and the reversal potential was -88 mV. The outward current was mimicked by an alpha(2)-adrenoceptor agonist, clonidine, and suppressed by an alpha(2)-adrenoceptor antagonist, yohimbine, but not by alpha(1)- and beta-antagonists. These findings suggest that NA acts on presynaptic sites to reduce noxious stimuli-induced EPSCs, and on postsynaptic SG neurones to induce an outward current by G-protein-mediated activation of K+ channels through alpha(2)-adrenoceptors, thereby producing an antinociceptive effect.