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Fred Rieke, Amy Lee, Françoise Haeseleer; Characterization of Ca2+-Binding Protein 5 Knockout Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(11):5126-5135. doi: 10.1167/iovs.08-2236.
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purpose. The goal of this study was to investigate, with the use of CaBP5 knockout mice, whether Ca2+-binding protein 5 (CaBP5) is required for vision. The authors also tested whether CaBP5 can modulate expressed Cav1.2 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 Cav1.2 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 Cav1.2 and colocalized with Cav1.2 in rod bipolar cells. In transfected HEK293T cells, CaBP5 suppressed calcium-dependent inactivation of Cav1.2 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 Cav1.2 by CaBP5 suggest that CaBP5 can alter retinal sensitivity through the modulation of voltage-gated calcium channels.
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