The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision

• DOI: 10.7554/elife.24550
• Publication Date: 2017-06-26T12:00:22Z
• Authors: Frans Vinberg; Tian Wang; Alicia De Maria; Haiqing Zhao; Steven Bassnett; Jeannie Chen; Vladimir J Kefalov
• Keywords: Primates; 0301 basic medicine; Vision; QH301-705.5; Knockout; Science; Inbred C57BL; Antiporters; Sodium-Calcium Exchanger; neuroscience; Mice; 03 medical and health sciences; Ocular; Animals; Biology (General); NCKX; mouse; Vision, Ocular; Zebrafish; Mice, Knockout; calcium; light adaptation; Q; R; photoreceptors; zebrafish; Mice, Inbred C57BL; color vision; retinal degeneration; Retinal Cone Photoreceptor Cells; Medicine; rhesus macaque; Neuroscience

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.