TY - JOUR
T1 - The Na+/Ca2+, K+ exchanger NCKX4 is required for efficient cone-mediated vision
AU - Vinberg, Frans
AU - Wang, Tian
AU - De Maria, Alicia
AU - Zhao, Haiqing
AU - Bassnett, Steven
AU - Chen, Jeannie
AU - Kefalov, Vladimir J.
N1 - Funding Information:
This work was supported by National Institutes of Health grants, EY027387 (VJK and JC), EY019312 and EY025696 (VJK), EY012155 (JC), EY026651 (FV), EY024607 (SB), DC007395 (HZ), and EY02687 (Washington University, Department Ophthalmology), Research to Prevent Blindness, and the Ella and Georg Ehrnrooth Foundation (FV). We thank Joseph Corbo for his initial insight into the possible expression of NCKX4 in cones. We also thank Jonathan Lytton from the University of Calgary for the Nckx2-/- mice and Janis Lem from Tufts University for the Gnat1-/- animal.
Publisher Copyright:
© 2017. Verasztó et al.
PY - 2017/6/26
Y1 - 2017/6/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85027102692&partnerID=8YFLogxK
U2 - 10.7554/eLife.24550
DO - 10.7554/eLife.24550
M3 - Article
C2 - 28650316
AN - SCOPUS:85027102692
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e24550
ER -