Presynaptic Cav3.2 channels regulate excitatory neurotransmission in nociceptive dorsal horn neurons.
Presynaptic Cav3.2 channels regulate excitatory neurotransmission in nociceptive dorsal horn neurons.
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DOI：
10.1523/jneurosci.0068-12.2012
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发表时间：
2012-07-04
期刊：
影响因子：
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通讯作者：
Todorovic SM
中科院分区：
文献类型：
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作者：
Jacus MO;Uebele VN;Renger JJ;Todorovic SM
突触前递质的释放主要受神经元高电压激活（HVA）钙通道亚型的调节。在这里的第一次，我们研究了T-型钙通道（T-通道）在突触传递中的作用，在脊髓背角（DH）使用膜片钳记录从大鼠和小鼠的急性脊髓准备。我们发现，选择性药理拮抗T-通道抑制自发突触释放谷氨酸在浅层I-II的DH，而GABA释放幸免。我们发现类似的效果，确定伤害性投射神经元的板层的DH，但不是在抑制DH中间神经元。相比之下，T通道的拮抗作用不影响更深的非伤害性DH板层的兴奋性传递。此外，我们使用同种型特异性试剂，敲除小鼠和免疫组织化学来特异性地暗示突触前CaV3.2通道。我们还使用了疼痛性糖尿病神经病变的动物模型，以证明阻断浅表DH神经元中的T通道在更大程度上抑制了糖尿病大鼠中自发兴奋性突触传递，而不是健康的年龄匹配的动物。这些研究提供了以前未知的信息突触前T通道在脊髓伤害性信号传导中的作用。
It is generally accepted that presynaptic transmitter release is mainly regulated by subtypes of neuronal high-voltage-activated (HVA) Ca2+ channels. Here for the first time, we examined the role of T-type Ca2+ channels (T-channels) in synaptic transmission in the dorsal horn (DH) of the spinal cord using patch-clamp recordings from acute spinal cord preparations from both rat and mouse. We found that selective pharmacological antagonism of T-channels inhibited spontaneous synaptic release of glutamate in superficial laminae I-II of the DH, while GABA release was spared. We found similar effect in identified nociceptive projection neurons of lamina I of the DH, but not in inhibitory DH interneurons. In comparison, antagonism of T-channels did not affect excitatory transmission in deeper non-nociceptive DH laminae. Furthermore, we used isoform-specific agents, knockout mice and immunohistochemistry to specifically implicate presynaptic CaV3.2 channels. We also used an animal model of painful diabetic neuropathy to demonstrate that blocking T-channels in superficial DH neurons suppressed spontaneous excitatory synaptic transmission in diabetic rats in greater degree than in healthy age-matched animals. These studies provide previously unknown information regarding the role of presynaptic T-channels in nociceptive signaling in the spinal cord.