α1-肾上腺素受体参与调控脊髓背角神经元突触传递的作用机制

The role of α1 adrenaline receptors on GABAergic and glutamatergic synapse in spinal dorsal horn

目的研究α1-肾上腺素受体(α1-AR)调控脊髓背角感觉神经元谷氨酸能突触传递的作用机制。方法在急性切取的腰段脊髓切片上,利用全细胞膜片钳法记录α1-AR激动剂苯肾上腺素对脊髓背角浅层神经元抑制性和兴奋性突触后电流(IPSCs和eEPSCs)的影响。结果苯肾上腺素对IPSCs频率产生剂量依赖性兴奋作用,此作用可被α1-AR特异性拮抗剂WB4101完全拮抗。苯肾上腺素对eEPSCs振幅的抑制作用可以部分被GABAA受体拮抗剂印防己毒素(picrotoxin,PTX)拮抗。结论位于脊髓背角神经元的α1-AR,促进初级传入纤维在脊髓背角释放γ-氨基丁酸(GABA),进而主要通过GABAA受体抑制初级传入纤维兴奋性谷氨酸能神经冲动的传入。下行肾上腺素能系统可能通过GABAA受体机制参与突触前对谷氨酸递质释放的调节作用。

Objective To investigate the role of oH-adrenaline receptors in GABAergic and glutamatergic synapses via GABAA receptors in spinal dorsal horn. Methods Using whole-cell vohage-α1amp recordings on acute spinal cord slice, the effect of blockade of α1-adrenaline receptors on GABAergic and glutamatergic synaptic transmission was studied. Results Selective α1-adrenline receptors agonist phenylephrine cold significantly increase the frequency of GABAergic spontaneous IPSCs in a concentration dependent manner, and this effect was abolished by the α1-adrenaline receptor an- tagonist WB4101. Phenylephrine also significantly reduced the amplitude of monosynaptic and polysynaptic EPSCs evoked from primary afferents. The inhibitory effect of phenylephrine on evoked monosynaptic glutamatergic EPSCs was largely blocked by the GABAA receptor antagonist picrotoxin. Conclusion Activation of α1- adrenoceptors in the spinal cord at- tenuates glutamatergic input from primary afferents mainly through GABAA receptors, indicating that presynaptic inhibition in the spinal cord may be involved in the regulation of nociception by the descending noradrenergic system.