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T.I. Rebrik, J.I. Korenbrot; In Mammals, Cones, but Not Rods, Demonstrate Ca2+-dependent Modulation of cGMP-gated Channels . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3181.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: In mammals cones adapt over a wide range of light intensities, but rods hardly adapt at all. In search of a molecular explanation for this observation we assessed Ca2+-dependent modulation of ligand sensitivity in cyclic-GMP gated (CNG) ion channels of intact mammalian rods and cones. Methods: Solitary photoreceptors were isolated by proteolytic treatment and mechanical disruption of ground squirrel retina. Rods and cones were specifically distinguished by their ability to bind, or not, PNA lectin. Using tight-seal electrodes, identified photoreceptors were loaded with Diazo-2, a caged Ca2+ buffer, a fixed concentration of 8Br-cGMP and PDE blockers Zaprinast or Sildenafil. Under voltage-clamp, we measured currents elicited by bright-flash uncaging of Diazo-2. Results: Sudden decrease in cytoplasmic Ca2+ caused by the uncaging flash resulted in a large, transient inward current in cones, but not at all in rods. Control experiments reveal the current changes reflect activation of CNG channels, in the presence of unchanging ligand concentration, and not other possible mechanisms, such as guanylyl cyclase activation or activation of Ca2+-dependent channels. Conclusions: In mammalian cones, but not rods, the activity of CNG channels is modulated by Ca2+ in the presence of constant ligand concentration. At levels of channel activity comparable to that measured in darkness, current enhancement due to channel modulation can be 3 to 5-fold in cones, but none is observed in rods. Channel modulation must be an important part of the mechanism of light adaptation in cones and its absence may explain the lack of adaptation in rods.
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