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Updated: Jul 4, 2026
Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina
Published on: May 6, 2015
Characterization of Ca2+-binding protein 5 knockout mouse retina
Fred Rieke1, Amy Lee, Françoise Haeseleer
1Department of 2Physiology and Biophysics, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Purpose:
The goal of this study was to investigate, with the use of CaBP5 knockout mice, whether Ca(2+)-binding protein 5 (CaBP5) is required for vision. The authors also tested whether CaBP5 can modulate expressed Ca(v)1.2 voltage-activated calcium channels.
Methods:
CaBP5 knockout (Cabp5(-/-)) mice were generated. The retinal morphology and visual function of 6-week-old Cabp5(-/-) mice were analyzed by confocal and electron microscopy, single-flash electroretinography, and whole-cell patch-clamp recordings of retinal ganglion cells. The interaction and modulation of Ca(v)1.2 channels by CaBP5 were analyzed using affinity chromatography, gel overlay assays, and patch-clamp recordings of transfected HEK293 cells.
Results:
No evidence of morphologic changes and no significant difference in the amplitude of the ERG responses were observed in CaBP5 knockout mice compared with wild-type mice. However, the sensitivity of retinal ganglion cell light responses was reduced by approximately 50% in Cabp5(-/-) mice. CaBP5 directly interacted with the CaM-binding domain of Ca(v)1.2 and colocalized with Ca(v)1.2 in rod bipolar cells. In transfected HEK293T cells, CaBP5 suppressed calcium-dependent inactivation of Ca(v)1.2 and shifted the voltage dependence of activation to more depolarized membrane potentials.
Conclusions:
This study provides evidence that lack of CaBP5 results in reduced sensitivity of rod-mediated light responses of retinal ganglion cells, suggestive of a role for CaBP5 in the normal transmission of light signals throughout the retinal circuitry. The interaction, colocalization, and modulation of Ca(v)1.2 by CaBP5 suggest that CaBP5 can alter retinal sensitivity through the modulation of voltage-gated calcium channels.
Insights
Calcium-binding protein 5 (CaBP5) is crucial for vision, as its absence reduces retinal ganglion cell light response sensitivity. CaBP5 modulates voltage-gated calcium channels, impacting visual signal transmission.
Area of Science:
- Neuroscience
- Molecular Biology
- Vision Science
Background:
- Calcium-binding protein 5 (CaBP5) is a protein involved in calcium signaling.
- Voltage-gated calcium channels, such as Ca(v)1.2, play critical roles in neuronal function, including in the retina.
- The precise role of CaBP5 in visual processing and its interaction with calcium channels remained unclear.
Purpose of the Study:
- To determine if CaBP5 is essential for normal vision using CaBP5 knockout mice.
- To investigate the potential modulatory effect of CaBP5 on Ca(v)1.2 voltage-activated calcium channels.
Main Methods:
- Generation and analysis of CaBP5 knockout (Cabp5(-/-)) mice.
- Assessment of retinal morphology and visual function via microscopy, electroretinography, and patch-clamp recordings.
- Investigation of CaBP5 and Ca(v)1.2 interactions using biochemical assays and electrophysiology in transfected cells.
Main Results:
- CaBP5 knockout mice showed no significant morphological or electroretinographic differences compared to wild-type.
- A ~50% reduction in the light response sensitivity of retinal ganglion cells was observed in CaBP5 knockout mice.
- CaBP5 directly interacts with Ca(v)1.2, colocalizes with it in rod bipolar cells, and suppresses its calcium-dependent inactivation.
Conclusions:
- CaBP5 deficiency leads to reduced sensitivity in rod-mediated light responses of retinal ganglion cells.
- CaBP5 plays a role in the normal transmission of light signals within the retinal circuitry.
- CaBP5 modulates Ca(v)1.2 channels, suggesting a mechanism for altering retinal sensitivity.
