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Clint L. Makino, Xiao-Hong Wen, Norman Michaud, Igor V. Peshenko, Basil Pawlyk, Richard S. Brush, Maria Soloviev, Xiaoqing Liu, Michael L. Woodruff, Peter D. Calvert, Andrey B. Savchenko, Robert E. Anderson, Gordon L. Fain, Tiansen Li, Michael A. Sandberg, Alexander M. Dizhoor; Effects of Low AIPL1 Expression on Phototransduction in Rods. Invest. Ophthalmol. Vis. Sci. 2006;47(5):2185-2194. doi: 10.1167/iovs.05-1341.
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purpose. To investigate the impact of aryl hydrocarbon receptor-interacting protein-like (AIPL)-1 on photoreception in rods.
methods. Photoresponses of mouse rods expressing lowered amounts of AIPL1 were studied by single-cell and electroretinogram (ERG) recordings. Phototransduction protein levels and enzymatic activities were determined in biochemical assays. Ca2+ dynamics were probed with a fluorescent dye. Comparisons were made to rods expressing mutant Y99C guanylate cyclase activating protein (GCAP)-1, to understand which effects arose from elevated dark levels of cGMP and Ca2+.
results. Except for PDE, transduction protein levels were normal in low-AIPL1 retinas, as were guanylate cyclase (GC), rhodopsin kinase (RK), and normalized phosphodiesterase (PDE) activities. Y99C and low-AIPL1 rods were more sensitive to flashes than normal, but flash responses of low-AIPL1 rods showed an abnormal delay, reduced rate of increase, and longer recovery not present in Y99C rod responses. In addition, low-AIPL1 rods but not Y99C rods failed to reach the normal light-induced minimum in Ca2+ concentration.
conclusions. Reduced AIPL1 delayed the photoresponse, decreased its amplification constant, slowed a rate-limiting step in its recovery, and limited the light-induced decrease in Ca2+. Not all changes were attributable to decreased PDE or to elevated cGMP and Ca2+ in darkness. Therefore, AIPL1 directly or indirectly affects more than one component of phototransduction.
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