title: The Na(+)/Ca(2+), K(+) exchanger 2 modulates mammalian cone phototransduction.
abstract: Calcium ions (Ca(2+)) 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 Ca(2+), which is then extruded back to the extracellular space. The mechanism of Ca(2+) extrusion from mammalian cones is not understood. The dominant view has been that the cone-specific isoform of the Na(+)/Ca(2+), K(+) exchanger, NCKX2, is responsible for removing Ca(2+) 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 Ca(2+) 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 Ca(2+) extrusion from mouse cones. However, surprisingly, Nckx2(-/-) cones adapted normally in steady background light, indicating the existence of additional Ca(2+)-extruding mechanisms in mammalian cones.
authors: Department of Ophthalmology and Visual Sciences, Washington University, Saint Louis, MO 63110, USA.
authors: Keisuke
authors: K
authors: Sakurai
authors: Department of Ophthalmology and Visual Sciences, Washington University, Saint Louis, MO 63110, USA.
authors: Frans
authors: F
authors: Vinberg
authors: Zilkha Neurogenetic Institute, Department of Cell and Neurobiology &Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors: Tian
authors: T
authors: Wang
authors: Zilkha Neurogenetic Institute, Department of Cell and Neurobiology &Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors: Jeannie
authors: J
authors: Chen
authors: Department of Ophthalmology and Visual Sciences, Washington University, Saint Louis, MO 63110, USA.
authors: Vladimir J
authors: VJ
authors: Kefalov
mesh_terms: D000221:Adaptation, Ocular / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004596:Electroretinography; D017353:Gene Deletion; D015870:Gene Expression; D006706:Homeostasis / Q000235:genetics; D017136:Ion Transport; D055537:Light Signal Transduction / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism
chemical_list: D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger; D012964:Sodium; D006152:Cyclic GMP; D002118:Calcium