The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision
The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision
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DOI：
10.7554/elife.24550
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发表时间：
2017-06-26
期刊：
影响因子：
7.7
通讯作者：
Kefalov, Vladimir J.
中科院分区：
文献类型：
--
作者：
Vinberg, Frans;Wang, Tian;Kefalov, Vladimir J.
钙（Ca 2+）在神经元的功能和健康中起着重要作用。在脊椎动物视锥细胞中，Ca 2+控制光反应敏感性、动力学和光适应。尽管Ca 2+在支持视锥细胞的功能和存活方面起着关键作用，但其从视锥细胞外节挤出的机制还不清楚。在这里，我们表明，Na+/Ca 2+，K+交换NCKX 4在斑马鱼，小鼠和灵长类动物的视锥细胞中表达。NCKX 4缺陷小鼠视锥细胞的功能分析表明，这种交换器对于视锥细胞介导的视觉的宽操作范围和高时间分辨率至关重要。我们发现NCKX 4与视锥细胞特异性NCKX 2一起塑造视锥细胞光反应：NCKX 4早期起作用以限制反应幅度，而NCKX 2晚期起作用以进一步加速反应恢复。视锥细胞中NCKX 4对Ca 2+的调节是一种新的机制，支持它们作为日间光感受器发挥作用并促进它们的存活。
Calcium (Ca2+) plays an important role in the function and health of neurons. In vertebrate cone photoreceptors, Ca2+ controls photoresponse sensitivity, kinetics, and light adaptation. Despite the critical role of Ca2+ in supporting the function and survival of cones, the mechanism for its extrusion from cone outer segments is not well understood. Here, we show that the Na+/Ca2+, K+ exchanger NCKX4 is expressed in zebrafish, mouse, and primate cones. Functional analysis of NCKX4-deficient mouse cones revealed that this exchanger is essential for the wide operating range and high temporal resolution of cone-mediated vision. We show that NCKX4 shapes the cone photoresponse together with the cone-specific NCKX2:NCKX4 acts early to limit response amplitude, while NCKX2 acts late to further accelerate response recovery. The regulation of Ca2+ by NCKX4 in cones is a novel mechanism that supports their ability to function as daytime photoreceptors and promotes their survival.