Lack of the sodium-driven chloride bicarbonate exchanger NCBE impairs visual function in the mouse retina.
Lack of the sodium-driven chloride bicarbonate exchanger NCBE impairs visual function in the mouse retina.
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DOI：
10.1371/journal.pone.0046155
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dedek K
中科院分区：
文献类型：
--
作者：
Hilgen G;Huebner AK;Tanimoto N;Sothilingam V;Seide C;Garcia Garrido M;Schmidt KF;Seeliger MW;Löwel S;Weiler R;Hübner CA;Dedek K
离子和pH稳态的调节对于正常神经元功能是必不可少的。钠驱动的氯碳酸氢盐交换器NCBE（Slc4a10）是碳酸氢盐转运蛋白SLC4家族的成员，利用钠的跨膜梯度来驱动细胞对碳酸氢盐的净摄取并挤出氯，从而调节神经元中的细胞内pH（pHi）和氯浓度（[Cl−]i）。在这里，我们表明，NCBE是强烈表达在视网膜。由于GABAA受体传导氯离子和碳酸氢根，我们假设NCBE可能与视网膜中的GABA能传递有关。重要的是，我们发现了一个差异表达的NCBE双极细胞：而NCBE的ON和OFF双极细胞轴突终端上表达，它只定位于树突的OFF双极细胞。在这些隔间，NCBE共定位与主要的神经元氯化物挤出机KCC2，这使得GABA超极化。NCBE也在星状无长突细胞中表达，但不存在于已知对GABA有反应的神经元中，如水平细胞。缺乏NCBE的小鼠在行为实验中表现出视力和对比敏感度下降，在视网膜电图中表现出b波振幅较小和潜伏期较长。NCBE缺陷小鼠的神经节细胞也显示出改变的时间响应特性。总之，我们的数据表明，NCBE可能有助于维持视网膜神经元细胞内的氯离子和碳酸氢根浓度。因此，视网膜中缺乏NCBE可能导致pHi调节和氯依赖性抑制的变化，导致信号传递改变和视觉功能受损。
Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10), a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pHi) and chloride concentration ([Cl−]i) in neurons. Here we show that NCBE is strongly expressed in the retina. As GABAA receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pHi regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function.
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影响因子：
4.4
作者：
Huber G;Beck SC;Grimm C;Sahaboglu-Tekgoz A;Paquet-Durand F;Wenzel A;Humphries P;Redmond TM;Seeliger MW;Fischer MD
通讯作者：
Fischer MD
影响因子：
2.5
作者：
Fox, Michael A.;Sanes, Joshua R.
通讯作者：
Sanes, Joshua R.
影响因子：
2.5
作者：
Dmitriev, AV;Mangel, SC
通讯作者：
Mangel, SC
影响因子：
16.2
作者：
Hübner, CA;Stein, V;Jentsch, TJ
通讯作者：
Jentsch, TJ
影响因子：
4.8
作者：
Haeseleer, F;Sokal, I;Palczewski, K
通讯作者：
Palczewski, K