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D. Krizaj, H. Yang, G. Nune, X. Liu, D.R. Copenhagen, B.L. Tempel, J.L. Duncan; The Timing And Amplitude Of Scotopic Visual Signals Are Regulated By Calcium Extrusion . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1141.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the regulation of the visual signal in the retina by the plasma membrane calcium ATPase isoform 2 (PMCA2). Methods: Retinas from deafwaddler (dfw2J) mice, in which the PMCA2 Ca transporter is not expressed, and wild type (wt) mice were investigated with anatomical methods, immunocytochemistry, electroretinograms (ERGs) and flash visual evoked potentials (FVEPs). Scotopic ERGs and FVEPs were recorded from anesthetized dfw2J and wt littermate mice after dark adaptation overnight at 1–2 months of age. Photopic ERGs were recorded after 10 minutes light adaptation. ERGs were also recorded from dfw2J and wt mice at 18 months of age. Results: Immunocytochemistry and Western blots showed PMCA2 was strongly expressed at birth as well as in adult wt retinae. The outer nuclear layer (ONL) and inner nuclear layer (INL) thickness of dfw2J and wt control mice were the same and the photoreceptor outer segments were normal in mice examined at both 1–2 and 18 months. However, scotopic a–wave and b–wave ERG responses were significantly smaller in amplitude (mean ± SEM a–wave: 294±30 vs 485±12 µV, p < 0.0001; b–wave 407±32 vs 849±23 µV, p<0.0001), and slower (a–wave 6.8±0.1 vs 6.1±0.1 msec, p<0.0001; b wave 107±2 vs 92±2 msec, p<0.0001) in dfw2J mutants vs wt controls. In contrast, photopic b–wave amplitudes were not significantly reduced (98±6 vs 114±6 µV, p=0.08), although photopic implicit times were significantly delayed in dfw2J mice vs wt (64±1 vs 60±1 msec, p=0.005). Four clearly defined oscillatory potentials (OPs) were identifiable in the ERG recordings of both dfw2J and wt mice. Overall, OP amplitudes were significantly smaller (F = 11.35, df = 1/138, p = 0.0015) and delayed (F = 38, df = 1/138; p <0.0001) in dfw2J vs wt mice. FVEP timing of dfw2J mice was significantly slower than wt (60±3 vs 49±2 msec, p<0.008). Conclusions: Our results reveal that PMCA2 plays a key role in controlling the amplitude and the synaptic latency at photoreceptor and amacrine synapses. Our data demonstrates that other PMCA isoforms can substitute for PMCA2 in development of the retina but cannot compensate for the role of PMCA2 in control of precise timing of the visual signal. We suggest this is due to much higher Ca affinity of PMCA2 compared to other PMCA isoforms. This is the first report showing that Ca extrusion can control timing in the CNS.
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