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B. G. Jeffrey, C. W. Morgans, R. M. Duvoisin; R9AP Modulates Activation of the Bipolar Cell Response as Measured in vivo With the ERG. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4185.
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© ARVO (1962-2015); The Authors (2016-present)
In photoreceptors, rhodopsin initiates a G-protein cascade which induces cation channel closure. In ON-bipolar cells (ON-BPCs), mGluR6 also couples a cation channel through G protein, Gαo. In the accompanying abstract (Morgans et al, ARVO 2007) we show that R9AP and the complexes Gß5-RGS7 and Gß5-RGS11 co-localize with mGluR6 in ON-BPC. We propose that R9AP-Gß5/RGS7 and/or R9AP-Gß5/RGS11 complexes accelerate the GTPase activity of Gαo, thus accelerating the opening of ON-BPC cation channels and the depolarizing response to light of bipolar cells. To test this hypothesis, the kinetics of the massed bipolar response in wild-type (WT) and R9AP-/- mice were measured in-vivo with the ERG.
After overnight dark-adaptation, scotopic full-field ERGs were recorded from 6 mice (3WT, 3 R9AP-/-) to brief flashes (0.7-3.2 log sc cd-s/m2). These intensities were sufficiently bright to rapidly drive the rods into saturation to maintain rods in saturation over the 1 sec recording epoch. Rod sensitivity and maximal rod response were derived from the fit of a P3 model to the leading edges of the ERG a-waves. Rod bipolar contributions (P2) were obtained by subtracting the P3 model from the ERGs and removing the oscillatory potentials with a filter. In order to study the kinetics of bipolar cell activation, an inverted P3 model was fit to the leading edge of the normalized P2 responses.
The kinetics activation of the bipolar cells measured from the P2 response were markedly slower for R9AP-/- mice compared with WT mice. For R9AP-/- mice, the slope of the rising phase of the P2 response was half that obtained for WT mice. Additionally, both the time to the onset of P2 response and the time to reach 50% of maximal amplitude were delayed in R9AP-/- mice and maximal P2 amplitude was more than 50% higher in R9AP-/- mice compared with WT mice. There were no differences between for R9AP-/- and WT mice for either rod sensitivity or maximal rod response.
Under scotopic conditions, glutamate release from photoreceptors activates a G-protein cascade in ON-BPCs that keeps these cells hyperpolarized. Thus the depolarizing light response of ON-BPCs requires the deactivation of the proteins in the G-protein cascade. The slower rising phase of P2 response in R9AP-/- mice in combination with the co-localization of R9AP and the Gß5-RGS7 and Gß5-RGS11 complexes with mGluR6 in ON-BPC dendritic tips argues that they function specifically in the mGluR6 signal transduction pathway and accelerate the opening of ON-BPC cation channels.
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