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J. Pahlberg, H. Okawa, L. Birnbaumer, F. Rieke, A. P. Sampath; Cooperative Control of Sensitivity by Two Splice Variants Of Go in Retinal Rod On-Bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4128.
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© ARVO (1962-2015); The Authors (2016-present)
The high sensitivity of scotopic vision is dependent on the efficient retinal processing of single photon responses generated by individual rods. At the first synapse in the mammalian retina rod outputs are pooled by rod bipolar cells, which use the mGluR6 signaling cascade to relay single photon responses. The mGluR6 receptor signals glutamate release through a heterotrimeric G-protein, Go, to close nonselective cation channels, recently identified to be TRPM1. However the effector in this pathway, or the gating particle controlling the TRPM1 current, remain unidentified. We investigate the role played by the splice variants of the G-protein, Gαo, in setting the properties of the light response in mouse rod bipolar cells.
Light-evoked currents in rod bipolar cells and AII amacrine cells were recorded by whole-cell patch-clamp techniques in mice lacking Gαo, or one of the splice variants, Gαo1 or Gαo2. Expressed protein levels were assessed using Western blotting.
Residual light responses were observed in rod bipolar cells of Gαo1-/- mice, but not Gαo-/- mice. These residual responses, attributable to Gαo2 , were 10-fold less sensitive than responses mediated by Gαo1 , and were driven by mGluR6 receptors. Rod bipolar responses in Gαo2-/- mice displayed a reduced sensitivity that was not influenced by reduced Gαo expression or the altered balance of expression level of Gαo1 vs. Gαo2 in Gαo1+/- mice. A halving of Gαo expression in Gαo+/- mice did not change the extent of saturation at the rod bipolar synapse.
Gαo1 and Gαo2 both mediate a depolarizing light response in rod bipolar cells allowing both to influence TRPM1 gating without occluding each other's actions, suggesting they might act at different sites on a common effector. These data indicate saturation within the mGluR6 signaling cascade that is critical for separating the rod single photon from rod noise must occur downstream of Gαo, and that Gαo2 works cooperatively with Gαo1 to improve the light sensitivity of rod bipolar cells.
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