Kainate Receptor-Mediated Responses in the CA1 Field of Wild-Type and GluR6-Deficient Mice
Kainate Receptor-Mediated Responses in the CA1 Field of Wild-Type and GluR6-Deficient Mice
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DOI：
10.1523/jneurosci.19-02-00653.1999
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发表时间：
1999-01
期刊：
影响因子：
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通讯作者：
I. Bureau;S. Bischoff;S. Heinemann;C. Mulle
中科院分区：
文献类型：
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作者：
I. Bureau;S. Bischoff;S. Heinemann;C. Mulle
红藻氨酸受体在海马体中大量表达。红藻氨酸受体亚单位的破坏小鼠允许遗传解剖的作用，每个红藻氨酸受体亚单位在海马的突触生理学，以及在兴奋性毒性过程。我们比较了domoate和kainate对野生型和GluR 6 −/−小鼠切片中CA 1锥体神经元的作用。野生型和GluR 6 −/−小鼠之间domoate和kainate诱发的内向电流幅度的差异表明CA 1锥体神经元中存在功能性kainate受体。AMPA受体拮抗剂2，3-二羟基-6-硝基-7-磺酰基-苯并（F）喹喔啉（1 μm）和1-（4-氨基苯基）-3-甲基氨甲酰基-4-甲基7，8-亚甲基二氧-3，4-二氢-5H-2，3-苯并二氮杂卓）（GYKI 53655）（50 μm）对多明戈酸激活的内向电流的阻断在GluR 6-/-小鼠中是完全的，但在野生型小鼠中仅部分。在存在GYKI 53655的情况下，红藻氨酸受体活化显著增加了野生型小鼠以及GluR 6 −/−小鼠的CA 1锥体细胞中自发IPSC的频率。这是由于红藻氨酸受体介导的持续内向电流激活和CA 1区传入GABA能中间神经元动作电位放电增加所致。这些效应在野生型以及GluR 6 −/−小鼠中观察到。红藻氨酸受体还通过增加野生型和GluR 6-/-小鼠中的突触失效来降低CA 1锥体细胞中诱发的IPSC的振幅。这些结果表明，在CA 1锥体细胞，红藻氨酸受体介导的几个功能拮抗作用的不同亚型。
Kainate receptors are abundantly expressed in the hippocampus. Mice with disruption of kainate receptor subunits allow the genetic dissection of the role of each kainate receptor subunits in the synaptic physiology of the hippocampus, as well as in excitotoxic processes. We have compared the action of domoate and kainate on CA1 pyramidal neurons in slices from wild-type and GluR6−/− mice. The difference in the amplitude of inward currents evoked by domoate and kainate between wild-type and GluR6−/− mice demonstrates the presence of functional kainate receptors in CA1 pyramidal neurons. Block of domoate-activated inward currents by the AMPA receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo(F)quinoxaline (1 μm) and 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine) (GYKI 53655) (50 μm) is complete in GluR6−/− mice but only partial in wild-type mice. In the presence of GYKI 53655, kainate receptor activation dramatically increases the frequency of spontaneous IPSCs in CA1 pyramidal cells from wild-type, as well as GluR6−/−, mice. This results from the kainate receptor-mediated activation of a sustained inward current and an increased action potential firing in afferent GABAergic interneurons of the CA1 field. These effects are observed in wild-type, as well as GluR6−/−, mice. Kainate receptors also decrease the amplitude of evoked IPSCs in CA1 pyramidal cells by increasing synaptic failures in wild-type and GluR6−/− mice. These results indicate that in CA1 pyramidal cells, distinct subtypes of kainate receptors mediate several functionally antagonistic effects.