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E.C. Solessio, G.A. Engbretson, Y. Umino, B.E. Knox, R.B. Barlow; Homeostasis in Constitutively Active Rods . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3717.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the metabolic requirements of constitutive activation in vitamin A–deprived rods. Understanding how photoreceptors respond to constitutive activity may reveal basic molecular mechanisms underlying cell death.
Xenopus laevis tadpoles were raised on a custom diet lacking vitamin A. Rod photocurrents were measured with suction electrode techniques. Phosphodiesterase activity was inferred from membrane current changes during exposure to IBMX solutions (IBMX jump method). Visual sensitivity was determined by assaying tadpole optomotor response to moving periodic patterns
We found that despite a 100–fold loss in sensitivity, constitutively active rods in vitamin A–deprived Xenopus develop extraordinarily high rates of cGMP synthesis (15–fold increase in basal rate) allowing them to maintain near normal circulating (dark) current densities and response ranges. The underlying compensatory changes come at the high metabolic cost of a 15–fold increase in basal ATP consumption by the phototransduction pathway. The rod outer segments in vitamin A–deprived rods are shorter and thinner than non–deprived rods while the thickness of the inner retina appears normal. Visual sensitivity tests suggest that, despite a loss in sensitivity, vitamin A–deprived rods maintain a threshold for transmission of visual information of 0.5–0.6 pA, the amplitude of the average single photon response in normal rods.
Preserving circulating current density and response range appears to be an important goal for rod homeostasis. However, the compensatory changes come at the high metabolic cost of a 15–fold increase in basal ATP consumption, which may drain the energetic resources of the cell restricting ATP available for disk morphogenesis and other "housekeeping" functions.
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