Bureau I, Bischoff S, Heinemann S F, Mulle C
Centre National de la Recherche Scientifique, Université Victor Segalen, Bordeaux 33076, France.
J Neurosci. 1999 Jan 15;19(2):653-63. doi: 10.1523/JNEUROSCI.19-02-00653.1999.
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 microM) and 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl7, 8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine) (GYKI 53655) (50 microM) 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.
海人藻酸受体在海马中大量表达。破坏海人藻酸受体亚基的小鼠使得对每个海人藻酸受体亚基在海马突触生理学以及兴奋性毒性过程中的作用进行遗传学剖析成为可能。我们比较了野生型和GluR6基因敲除小鼠脑片中多莫酸和海人藻酸对CA1锥体神经元的作用。野生型和GluR6基因敲除小鼠之间多莫酸和海人藻酸诱发的内向电流幅度差异表明CA1锥体神经元中存在功能性海人藻酸受体。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微摩尔）和1 - (4 - 氨基苯基)-3 - 甲基氨基甲酰基 - 4 - 甲基 - 7,8 - 亚甲基二氧基 - 3,4 - 二氢 - 5H - 2,3 - 苯并二氮杂卓（GYKI 53655）（50微摩尔）对多莫酸激活的内向电流的阻断在GluR6基因敲除小鼠中是完全的，但在野生型小鼠中只是部分的。在存在GYKI 53655的情况下，海人藻酸受体激活显著增加野生型以及GluR6基因敲除小鼠CA1锥体细胞中自发抑制性突触后电流（IPSCs）的频率。这是由于海人藻酸受体介导的持续性内向电流激活以及CA1区传入GABA能中间神经元动作电位发放增加所致。在野生型以及GluR6基因敲除小鼠中均观察到了这些效应。海人藻酸受体还通过增加野生型和GluR6基因敲除小鼠中的突触传递失败来降低CA1锥体细胞中诱发的IPSCs的幅度。这些结果表明，在CA1锥体细胞中，不同亚型的海人藻酸受体介导了几种功能上相互拮抗的效应。
