Glutamate transporters EAAT4 and EAAT5 are expressed in vestibular hair cells and calyx endings.

Glutamate transporters EAAT4 and EAAT5 are expressed in vestibular hair cells and calyx endings.
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DOI:
10.1371/journal.pone.0046261
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Chabbert C
Chabbert C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dalet A;Bonsacquet J;Gaboyard-Niay S;Calin-Jageman I;Chidavaenzi RL;Venteo S;Desmadryl G;Goldberg JM;Lysakowski A;Chabbert C

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谷氨酸是毛细胞释放的神经递质。它从突触间隙中清除可以塑造神经传递并防止兴奋性毒性。这在内耳和其他感觉器官中可能特别重要,因为那里有持续高速率的神经递质释放。在大多数耳蜗和II型前庭毛细胞的情况下,清除涉及谷氨酸扩散到支持细胞,在那里它被谷氨酸转运蛋白EAAT 1(GLAST)吸收。类似的机制不能在前庭I型毛细胞中起作用,因为萼末端的存在将支持细胞与毛细胞突触分开。由于这种排列,已经证实谷氨酸转运体必须存在于I型毛细胞、萼末端或两者中。使用全细胞膜片钳记录,我们表明,谷氨酸激活的阴离子电流,归因于高亲和力谷氨酸转运蛋白和DL-TBOA阻断,在I型毛细胞中表达,但不在II型毛细胞中。分子研究表明,EAAT 4和EAAT 5,两个谷氨酸转运体,可能是负离子电流的基础,在I型和II型毛细胞和萼末端表达。EAAT 4被认为几乎仅在小脑中表达,而EAAT 5在视网膜中表达。我们的研究结果表明,这两种转运蛋白在小鼠中有更广泛的分布。这是第一次证明毛细胞中存在转运蛋白,并提供了突触前元件中EAAT的少数例子之一。
Glutamate is the neurotransmitter released from hair cells. Its clearance from the synaptic cleft can shape neurotransmission and prevent excitotoxicity. This may be particularly important in the inner ear and in other sensory organs where there is a continually high rate of neurotransmitter release. In the case of most cochlear and type II vestibular hair cells, clearance involves the diffusion of glutamate to supporting cells, where it is taken up by EAAT1 (GLAST), a glutamate transporter. A similar mechanism cannot work in vestibular type I hair cells as the presence of calyx endings separates supporting cells from hair-cell synapses. Because of this arrangement, it has been conjectured that a glutamate transporter must be present in the type I hair cell, the calyx ending, or both. Using whole-cell patch-clamp recordings, we demonstrate that a glutamate-activated anion current, attributable to a high-affinity glutamate transporter and blocked by DL-TBOA, is expressed in type I, but not in type II hair cells. Molecular investigations reveal that EAAT4 and EAAT5, two glutamate transporters that could underlie the anion current, are expressed in both type I and type II hair cells and in calyx endings. EAAT4 has been thought to be expressed almost exclusively in the cerebellum and EAAT5 in the retina. Our results show that these two transporters have a wider distribution in mice. This is the first demonstration of the presence of transporters in hair cells and provides one of the few examples of EAATs in presynaptic elements.
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