TY - JOUR
T1 - The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction
AU - Sakurai, Keisuke
AU - Vinberg, Frans
AU - Wang, Tian
AU - Chen, Jeannie
AU - Kefalov, Vladimir J.
N1 - Funding Information:
This work was supported by National Institutes of Health grants, EY19543 and EY19312 (V.J.K.), EY12155 (J.C.), EY026651 (F.V.), and EY02687
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Calcium ions (Ca2+) modulate the phototransduction cascade of vertebrate cone photoreceptors to tune gain, inactivation, and light adaptation. In darkness, the continuous current entering the cone outer segment through cGMP-gated (CNG) channels is carried in part by Ca2+, which is then extruded back to the extracellular space. The mechanism of Ca2+ extrusion from mammalian cones is not understood. The dominant view has been that the cone-specific isoform of the Na+Ca2+, K+ exchanger, NCKX2, is responsible for removing Ca2+ from their outer segments. However, indirect evaluation of cone function in NCKX2-deficient (Nckx2-/-) mice by electroretinogram recordings revealed normal photopic b-wave responses. This unexpected result suggested that NCKX2 may not be involved in the Ca2+ homeostasis of mammalian cones. To address this controversy, we examined the expression of NCKX2 in mouse cones and performed transretinal recordings from Nckx2-/- mice to determine the effect of NCKX2 deletion on cone function directly. We found that Nckx2-/- cones exhibit compromised phototransduction inactivation, slower response recovery and delayed background adaptation. We conclude that NCKX2 is required for the maintenance of efficient Ca2+ extrusion from mouse cones. However, surprisingly, Nckx2-/- cones adapted normally in steady background light, indicating the existence of additional Ca2+-Extruding mechanisms in mammalian cones.
AB - Calcium ions (Ca2+) modulate the phototransduction cascade of vertebrate cone photoreceptors to tune gain, inactivation, and light adaptation. In darkness, the continuous current entering the cone outer segment through cGMP-gated (CNG) channels is carried in part by Ca2+, which is then extruded back to the extracellular space. The mechanism of Ca2+ extrusion from mammalian cones is not understood. The dominant view has been that the cone-specific isoform of the Na+Ca2+, K+ exchanger, NCKX2, is responsible for removing Ca2+ from their outer segments. However, indirect evaluation of cone function in NCKX2-deficient (Nckx2-/-) mice by electroretinogram recordings revealed normal photopic b-wave responses. This unexpected result suggested that NCKX2 may not be involved in the Ca2+ homeostasis of mammalian cones. To address this controversy, we examined the expression of NCKX2 in mouse cones and performed transretinal recordings from Nckx2-/- mice to determine the effect of NCKX2 deletion on cone function directly. We found that Nckx2-/- cones exhibit compromised phototransduction inactivation, slower response recovery and delayed background adaptation. We conclude that NCKX2 is required for the maintenance of efficient Ca2+ extrusion from mouse cones. However, surprisingly, Nckx2-/- cones adapted normally in steady background light, indicating the existence of additional Ca2+-Extruding mechanisms in mammalian cones.
UR - http://www.scopus.com/inward/record.url?scp=84986216122&partnerID=8YFLogxK
U2 - 10.1038/srep32521
DO - 10.1038/srep32521
M3 - Article
C2 - 27580676
AN - SCOPUS:84986216122
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 32521
ER -