Department of Functional Morphology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.
Neuroscience. 2010 Mar 10;166(1):305-11. doi: 10.1016/j.neuroscience.2009.12.007. Epub 2009 Dec 23.
Glutamate AMPA receptors are critical for sensory transmission at the spinal cord dorsal horn (DH). Plasma membrane AMPA receptor endocytosis that can be induced by insulin may underlie long term modulation of synaptic transmission. Insulin receptors (IRs) are known to be expressed on spinal cord DH neurons, but their possible role in sensory transmission has not been studied. In this work the effect of insulin application on fast excitatory postsynaptic currents (EPSCs) mediated by AMPA receptors evoked in DH neurons was evaluated. Acute spinal cord slices from 6 to 10 day old mice were used to record EPSCs evoked in visually identified superficial DH neurons by dorsal root primary afferent stimulation. AMPA EPSCs could be evoked in all of the tested neurons. In 75% of the neurons the size of the AMPA EPSCs was reduced to 62.1% and to 68.9% of the control values when 0.5 or 10 microM insulin was applied. There was no significant change in the size of the AMPA EPSCs in the remaining 25% of DH neurons. The membrane permeable protein tyrosine kinase inhibitor, lavendustin A (10 microM), prevented the insulin induced AMPA EPSC depression. Our results suggest a possible role of the insulin pathway in modulation of sensory and nociceptive synaptic transmission in the spinal cord.
谷氨酸 AMPA 受体在脊髓背角（DH）的感觉传递中至关重要。胰岛素可诱导的质膜 AMPA 受体内吞作用可能是突触传递长时程调制的基础。已知胰岛素受体（IR）在脊髓 DH 神经元上表达，但它们在感觉传递中的可能作用尚未研究。在这项工作中，评估了胰岛素应用对 DH 神经元中 AMPA 受体介导的快速兴奋性突触后电流（EPSC）的影响。使用来自 6 至 10 天大的小鼠的急性脊髓切片，通过背根初级传入刺激记录在视觉鉴定的浅层 DH 神经元中诱发的 EPSC。可以在所有测试的神经元中诱发出 AMPA EPSC。在 75％的神经元中，当施加 0.5 或 10 μM 胰岛素时，AMPA EPSC 的大小减小至对照值的 62.1％和 68.9％。在剩余的 25％DH 神经元中，AMPA EPSC 的大小没有明显变化。膜可渗透的蛋白酪氨酸激酶抑制剂 lavendustin A（10 μM）可防止胰岛素诱导的 AMPA EPSC 抑制。我们的结果表明，胰岛素途径可能在脊髓中调节感觉和伤害性突触传递中起作用。
