The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction

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...

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Main Authors:	Sakurai, Keisuke, Vinberg, Frans, Wang, Tian, Chen, Jeannie, Kefalov, Vladimir J.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007492/

id	pubmed-5007492
recordtype	oai_dc
spelling	pubmed-50074922016-09-07 The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction Sakurai, Keisuke Vinberg, Frans Wang, Tian Chen, Jeannie Kefalov, Vladimir J. Article 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. Nature Publishing Group 2016-09-01 /pmc/articles/PMC5007492/ /pubmed/27580676 http://dx.doi.org/10.1038/srep32521 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sakurai, Keisuke Vinberg, Frans Wang, Tian Chen, Jeannie Kefalov, Vladimir J.
spellingShingle	Sakurai, Keisuke Vinberg, Frans Wang, Tian Chen, Jeannie Kefalov, Vladimir J. The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction
author_facet	Sakurai, Keisuke Vinberg, Frans Wang, Tian Chen, Jeannie Kefalov, Vladimir J.
author_sort	Sakurai, Keisuke
title	The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction
title_short	The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction
title_full	The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction
title_fullStr	The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction
title_full_unstemmed	The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction
title_sort	na+/ca2+, k+ exchanger 2 modulates mammalian cone phototransduction
description	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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007492/
_version_	1613640795552743424

The Na+/Ca2+, K+ exchanger 2 modulates mammalian cone phototransduction

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